CONTROL OF TGF beta SIGNALING BY km23 SUPERFAMILY MEMBERS

Abstract: The present invention provides pharmaceutical compositions including a polypeptide mediator of the signal transduction activity of TGF beta superfamily members (km23) and the nucleic acid forms which identify and encode km23. The invention also provides human km23 polypeptides, fragments and mutants thereof, oligonucleotides and primers directed to km23 nucleic acid forms, expression vectors, host cells, agonists, antibodies, antagonists and their use for the diagnosis, prevention and treatment of diseases associated with the expression or activity of km23, or with defects in the signaling pathway for TGF beta superfamily members. Furthermore, the invention relates to mutations in the km23 gene in human cancers and their use in the diagnosis and prognosis of human cancer. Specific mutations in the km23 gene associated with ovarian cancers have been identified.

Description: CONTROL OF TGFβ SIGNALING BY km23 SUPERFAMILY MEMBERS FIELD OF THE INVENTION: The present invention relates generally to isolated or recombinant polypeptides, or fragments thereof, which function in growth factor or cytokine signaling pathways. More specifically, the present invention relates to the specific family of polypeptides, or fragments thereof, termed km23, and its various forms, which interact with TGFβ receptors and/or are present in a signaling pathway for TGFβ superfamily members. The km23 family members of the present invention are molecular targets against which therapeutics can be designed by molecular, immunological or pharmacological approaches, or for detection, diagnosing, or determining the prognosis of patients with abnormal growth control. BACKGROUND OF THE TNVENTON: The publications and other materials used herein to illuminate the background of the invention, and in particular to provide additional details relating to the invention, are referenced in the following text and are grouped in the appended list of references. Transforming growth factor β's (TGFβ) are one of the few natural growth inhibitors which inhibit the growth of most epithelial cells. In contrast to other inhibitors, TGFβ is generally non cytotoxic, even at concentrations which are orders of magnitude above its effective concentration. TGFβ is the prototype for over 40 family members which share structural and functional similarities. The TGFβ superfamily plays an essential role in almost every aspect of cellular processes, including early embryonic development, cell growth, differentiation, cell motility, and apoptosis. See for example Yue and Mulder (2001); Sporn and Vilcek (2000); Massaque (1998); and Hartsough and Mulder (1997). The ability of TGFβ to potently inhibit the growth of many epithelial cells and solid tumors of epithelial origin, i.e. colon, breast, prostrate, lung, liver, ovarian, etc. is well established. However, many solid tumors develop resistance to the growth inhibitory effects of TGFβ. When cells become resistant to TGFβ, they no longer have the natural growth check provided by TGFβ and, as a result, may proliferate continually. Thus, TGFβ plays an important role in tumorigenesis and tumor aggressiveness. This resistance to TGFβ-mediated growth inhibition may occur at many levels. For example, the tumor cells may become unable to activate latent TGFβ (see for example, Wakefield et al. (1987); and Sporn et al., (1987), may display mutations in signaling receptors (Kim et al, 2000), or may develop defective TGFβ signaling pathways (Hartsough and Mulder, 1997). TGFβ interacts with two major signaling receptors, designated RI and RII. The current working model for activation of the TGFβ receptors involves TGFβ binding by RII, which is constitutively phosphorylated. RU recruits RI into a complex (TβR complex) and phosphorylates RI in its GS domain. The complex then propagates the signal, presumably by interacting with and/or phosphorylating downstream cytoplasmic components (Wrana et al., 1994). TGFβ RI and RII are mutated in human cancer cells (Massague, 1998). Mutations in TGFβ type II receptors are most common, particularly in human colon and gastric cancers; these are associated with microsatellite instability and a loss of TGFβ responsiveness (Markowitz et al, 1995). In addition, gross structural defects in the RII gene, as well as alterations in transcriptional repression of RII, contribute to a loss of TGFβ responsiveness (Kim et al, 2000). Although alterations in TGFβ RI receptors are less common, transcriptional repression of RI may be an alternative mechanism for subverting the growth inhibitory response to TGFβ. Other more subtle alterations in RI may also exist (Kim et al., 2000). However, if normal TGFβ receptors are expressed in cells with mutated receptors, TGFβ responsiveness does not always return. Thus, signal transduction pathways must also be altered. Several types of signaling components have been described as participants in TGFβ signaling. These include protein kinase C (PKC), phospholipase C, protein phosphatase 1, Ras, several mitogen-activated protein kinases (Mapks), the Smads, and some of the Rho family members (Hartsough and Mulder, 1997; Mulder, 2000). Aside from the Ras/Mapk and Smad pathways, however, the generality and biological significance of the other components in the TGFβ pathway is unclear. It has been demonstrated that TGFβ activates Ras within 3-6 min in untransformed epithelial cells that are TGFβ-sensitive, but not in cells that are TGFβ- resistant (Mulder and Morris, 1992). Several mitogen-activated protein kinases (Mapks) are also rapidly activated (within 5-30 min) after addition of TGFβ (Hartsough and Mulder, 1995; Frey and Mulder, 1997). The activation of some of the Mapks is sustained, indicative of nuclear translocation of the protein and subsequent regulation of transcription. The rapid kinetics for these effects indicate that they are direct, and not the consequence of the release of other growth factors that could subsequently regulate the Ras Mapk pathways. It has also been shown that activation of Ras by TGFβ is required for the regulation of various cell cycle proteins in the nucleus (Yue et al., 1998). More recently, it has become clear that TGFβ activation of these pathways is required for transcriptional regulation of TGFβ itself, and the resulting autoproduction of TGFβ (Yue and Mulder, 2000) . The Smad superfamily are highly conserved proteins which include the Drosophila MAD and DAD proteins, three C. elegans proteins, a few xenopus proteins, and nine mammalian Smad isoforms (reviewed in Wrana and Attisano, 2000; Miyazono, 2000). Based upon accumulating evidence pertaining to the Smads, a general model for Smad function has been proposed. The so-called "receptor activated" RSmads (i.e., Smads 1-3 and 5) are phosphorylated after receptor activation and form a complex with the Smad 4 type components (common-partner Smad or co-Smad). Smad 4/dpc4 itself is not phosphorylated, but its heterocomplex formation with the other Smads is thought to mediate translocation of Smads to the nucleus and transcriptional activation. Over the past years, progress has been made in identifying signal transduction components activated by TGFβ superfamily members. However, even though various signaling proteins have been analyzed, the cytoplasmic pathways regulated by TGFβ are still very poorly understood. It should be noted that discovery of TGFβ signaling components which are essential for mediating the biological responses of TGFβ has been difficult. For example, Smads were identified based upon homology screens using the Drosophila or C. elegans cDNAs. It is further noted that both the Smad and the Ras Mapk pathways regulate transcriptional events. Clearly, TGFβ has functions in addition to transcriptional regulation. Thus, there is a need for identifying components which play a role in TGFβ signaling and/or regulate cellular events in addition to transcription. Several potential TGFβ signaling components have been identified based upon their interaction with TGFβ receptors. Initial studies led to the identification of FKBP12 and the alpha subunit of farnesyl transferase as TGFβ RI interactors, TREP-l as an Rll-interacting protein, and clusterin (also called apolipoprotein J) as a component that interacts with both TGFβ receptors. (See for example, Kawabata et al., 1995; Ventura et al., 1996; Reddy et al., 1996). Additional studies led to the discovery of TRAP- 1 as an interactor of the constitutively active triple RI mutant (LI 93 A, PI 94 A, T204D) and STRAP (a WD-domain protein) as a component that associates with both RI and RII (See for example, Charng et al., 1998; Datta et al., 1998). Another WD domain protein that interacts with TGFβ RI was identified as the B α subunit of protein phosphatase 2A (See for example, Griswold-Prenner et al., 1998). However, the functional significance of these factors is, at present, unclear. Various Smad-interacting proteins have also been identified, including SARA, which interacts with both Smads and TGFβ receptors (See for example, Tsukazaki et al., 1998). Several of the Smad-interacting factors have been shown to function as transcriptional repressors or co-activators (See for example, Massague and Chen, 2000; Hata et al, 2000). These factors address the transcriptional functions of TGFβ. However, they do not explain or provide insight into how TGFβ accomplishes the diverse activities which make it a multi-functional polypeptide. In addition, the alterations found thus far in these signaling components do not explain the diverse types of cancers that arise from a loss of growth control related to TGFβ or its signaling pathways. Thus, it is clear that there are additional TGFβ signaling components and pathways which are important to the complete understanding of how TGFβ asserts its growth suppressive and other functions inside cells and how these pathways are subverted to result in epithelial cancers. Since TGFβ plays a critical role in such a vast array of human pathologies, any factor in one of TGFβ' s signaling pathways is sure to have therapeutic potential for one or more of these diseases. These human pathologies include cancer, atherosclerosis, restenosis, arteriosclerosis, diabetic kidney disease, glomerulosclerosis, most progressive renal disorders, other sclerotic diseases, stroke, chronic inflammation, arthritis, hyperreactivity of the lymphoid system, asthma, periodontal disease, glaucoma, pulmonary fibrosis, other fibrotic diseases, scarring during wound healing, osteoporosis, neurodegenerative diseases, ischemic injury, encephalomyelitis, autoimmunity, immunodeficiencies, and other immune mediated-pathologies (See Sporn and Vilcek, 2000). Of particular interest, TGFβ has been shown to be a tumor suppressor displaying true haploid insufficiency in its ability to protect against tumorigenesis (Tang et al. 1998). Many of the signaling components identified in the TGFβ signaling pathway have also been shown to function as tumor suppressors. Nothwithstanding new technologies, aggressive surgery, and modern chemotherapy, there has been little change in the survival of cancer patients having specific types of cancers over the past several years. The genetics of cancer is complicated, involving multiple dominant, positive regulators of the transformed state (oncogenes) as well as multiple recessive, negative regulators (tumor suppressor genes). Over 100 oncogenes have been characterize thus far. However, fewer than a dozen tumor suppressor genes have been identified, although the number is expected to increase significantly (Knudson, 1993). The involvement of so many genes underscores the complexity of the growth control mechanisms that operate in cells to maintain the integrity of normal tissue. So far, no single gene has been shown to participate in the development of all, or even the majority, of human cancers. The most frequently mutated tumor suppressor gene is the p53 gene, mutated in roughly 50% of all tumors. The hope for a new generation of specifically targeted anti-tumor therapeutics may rest upon the ability to identify tumor suppressor genes that play important roles in the control of cell division. TGFβ receptor-interacting proteins or components of TGFβ superfamily member signaling pathways are likely to represent potential tumor suppressor genes. Dynein is a molecular motor protein which mediates intracellular transport; it conveys its cargo along polarized microtubules (MTs) toward the minus ends. It is a massive multisubunit complex composed of heavy chains (HC's), intermediate chains (IC's), light intermediate chains (LIC's), light chains (LC's), and IC/LC-associated proteins (Hirokawa, 1998). The MT-binding domain is located within the HC's that form the globular heads and stems of the complex, whereas cargo-binding activity involves the IC's and several classes of LC's that associate at the base of the soluble dynein particle. Evidence also exists to suggest that the IC/LC complexes have a distinct and stable structure (King, 2000). Dynein superfamily members appear to control various cell functions which include axonal transport, flagellar motility, organization of the mitotic spindle, distribution of late endosomes and lysosomes, the centrosomal localization of the Golgi complex, vesicular transport from early to late endosomes, the apical transport of Golgi-derived membranes in epithelial cells, the movement of phagosomes, and others (see for example, in Hirokawa, 1998). However, little is known about the regulation of the movement that the dynein motors drive. A large number of cytoplasmic dynein- associated proteins with diverse structural and functional roles have been identified (Milisav, 1998). However, it remains obscure as to the requirement by dynein of so many associated LC's, and LC/IC-associated proteins. A new family of dynein-associated proteins which are both Drosophila roadblock (robl)-like, Chlamydomonas dynein light chain (LC)-like, and Drosophila bithoraxoid (bxd)-like have been described (Bowman et al., 1999). The original Drosophila bithoraxoid (bxd) gene of this family has been described in detail, but the transcripts are not encoded into protein (Lipshitz et al., 1987). Bxd is actually part of a huge bithorax gene complex (BX-C) which plays a role in segment development in Drosophila (Morata and Kerridge 1981; Smolik-Utlaut 1990; Stern, 1998). However, no functional studies have been reported with regard to bxd-like encoded proteins. km23 has 67% homology with robl and is identical to the class 1 mammalian robl-like proteins thought to play a role in cytoplasmic dynein functions. Accordingly, these results suggest that km23 is most likely a dynein-associated protein which plays an important role in MT dynamics. Our data indicate that this is, indeed, the case. However, more importantly, our discovery of km23 as a TGFβ-receptor interactor and a dynein-interactor establishes the first connection between growth factor receptors and minus end MT dynamics, and indicates that such receptors can regulate dynein- mediated MT functions. Although a recent report has described MTs as a cytoplasmic sequestering network for the Smads (Dong et al., 2000), these results again focus on the transcriptional functions of TGFβ. In this context, MTs appear to function by negatively regulating Smad transcriptional responses. However, no direct studies have been performed to determine how TGFβ may regulate MTs to induce the mtracellular transport of specific proteins, and/or to mediate the diverse functions of TGFβ. MTs are 25-nm tubule-like structures composed of alpha- and beta-tubulin heterodimers (reviewed in Hirokawa, 1998). Several parallel protofilaments composed of linearly arranged heterodimers form the MT wall, to which MT-associated proteins and motor proteins bind. MTs are polar structures with a fast-growing plus end and a minus end. They function as "rails" for the transport of organelles via MT-associated motor proteins such as dynein. MTs are important for many cellular processes, and play an important role in the generation and maintenance of epithelial cell polarity (Hofer et al., 1998). Outer arm dynein-associated proteins interact with dynein at the base of the dynein particle, as well as possibly with other proteins present in the cytoplasmic dynein complex (Bowman et al., 1999). However, it is unclear whether growth factors such as TGFβ can regulate dynein MT transport. The sum total of distinct, yet interacting, signaling pathways that are activated simultaneously after TGFβ receptor activation, will play a significant role in both the normal growth of cells and in a variety of critical pathological conditions. Accordingly, identification of additional TGFβ signaling components and pathways will greatly advance our overall understanding of mtracellular targets that dictate the fate of the organism. Thus, a need in the art exists for the discovery of TGFβ receptor- interacting proteins or TGFβ signaling components, and the polynucleotides encoding them, in order to provide new compositions which are useful in the diagnosis, prevention, and treatment of disorders associated with cancer and other diseases the development and progression in which TGFβ has been implicated. SUMMARY OF THE INVENTION: The present invention provides for an isolated or recombinant km23 polypeptide in a pharmaceutical composition suitable for humans, wherein the polypeptide functions in a growth factor or cytokine signaling pathway. The invention further provides for an isolated or recombinant km23 polypeptide fragment, including protein fragments, which function in a growth factor or cytokine signaling pathway. In particular, the present invention is based on the ability of the km23 protein generally represented by the formula SEQ ID NO: 1 or SEQ ID NO: 2 to mediate the signal transduction activity of the TGFβ superfamily of growth factors. The invention further relates to mutations in the km23 gene which result in the production of mutant km23 polypeptides and their use in the diagnosis of predisposition to several cancers, including but not limited to, ovarian cancer. In particular, the invention provides a mutant km23 polypeptide which modulates a growth factor or cytokine signaling pathway. Moreover, the invention provides for a cloned mutant km23 nucleic acid form, which modulates a growth factor or cytokine signaling pathway. For example, the mutant may be characterized by a mutation of at least one nucleotide base relative to a wild-type km23 nucleic acid form, which mutation results in a mutant km23 polypeptide described above. The invention also relates to a fusion protein including a km23 polypeptide or a mutant form thereof and a second polypeptide having an amino acid sequence unrelated to the amino acid sequence of the km23 polypeptide or mutant form. Moreover, a cloned nucleic acid molecule encoding the fusion protein is further provided herein. An expression vector capable of expressing in a host cell a km23 polypeptide or fragment thereof and its use in protein replacement therapy and protein mimetics is further provided herein. Moreover, a host cell transfected with the expression vector, wherein the host cell is capable of expressing the km23 polypeptide or fragment is further provided. The invention also relates to a substantially pure oligonucleotide or primer, the oligonucleotide or primer including a region of nucleotide sequence capable of hybridizing under stringent conditions to at least about twelve consecutive nucleotides of sense or anti-sense sequence of a km23 nucleic acid form according to this invention and the use of such oligonucleotides or primers in the diagnosis and prognosis of hyper- proliferative disorders and in gene therapy. The invention further provides for various methods of use of the km23 polypeptides, fragments, mutants thereof, and km23 nucleic acid forms described herein. For example, the invention provides for a method of modulating intracellular signal transduction pathways mediated by TGFβ superfamily members, the method including introducing into the cell a km23 polypeptide, where the polypeptide may include, but is not limited to, the amino acid sequence represented in the general formulas of SEQ ID NO: 1 or SEQ ID NO: 2, as well as fragments thereof. Further provided herein is the method of modulating intracellular signal transduction pathways mediated by TGFβ superfamily members, the method including introducing into the cell an agonist of a km23 nucleic acid form or an agonist of amino acids encoded by the nucleic acid form. Further encompassed by the present invention is a method of modulating intracellular signal transduction pathways mediated by TGFβ superfamily members, the method including introducing into the cell an antagonist of a km23 nucleic acid form, or a mutant thereof, or an antagonist of amino acids encoded by the nucleic acid form. A method for identifying therapeutic agents that inhibit, potentiate, or mimic the ability of a km23 polypeptide, or a mutant thereof, or a nucleic acid encoding the polypeptide to modulate the signal transduction activity of at least one member of the TGFβ superfamily of growth factors is provided by this invention, the method including: (a) treating a cell with an effective amount of at least one candidate so as to alter at least one of regulation of gene expression, cell growth, cell differentiation, cell survival, apoptosis, senescence, cell migration, angiogenesis, fibrosis, wound healing, extracellular matrix induction, adhesion, autoproduction, embryogenesis and combinations thereof; and (b) and measuring the effect of the candidate on the cell. Furthermore, a method for identifying therapeutic agents that inhibit, potentiate or mimic the ability of a km23 polypeptide, or a mutant thereof, or a nucleic acid encoding the polypeptide to modulate the signal transduction activity of at least one member of the TGFβ superfamily of growth factors is provided, the method including: (a) treating a cell with an effective amount of at least one candidate so as to alter at least one of actin cytoskeleton dynamics, microtubule dynamics, intracellular transport, cell polarity, dynein-mediated microtubule transport and combinations thereof; and (b) measuring the effect of the candidate on the cell. The invention further encompasses a method of restoring the growth inhibitory activity of TGFβ superfamily members, the method including introducing into the cell an antagonist of a mutant km23 form, wherein the mutant form blocks the growth inhibitory activity of the TGFβ superfamily member, and wherein the antagonist is a therapeutic agent. Further provided are several methods relating to the prognosis and diagnosis for a patient who is at risk for a disorder or has a disorder. For example, the present invention provides for a method of determining if a patient is at risk for a disorder or has a disorder, the method including detecting in a patient specimen the presence or absence of a lesion characterized by an alteration in sequence, expression, post- translational modification, or some combination thereof of km23 nucleic acid or polypeptide forms. One diagnostic method provided by the invention is for detecting a km23 nucleic acid form in a biological sample, the method including hybridizing km23 nucleic acid forms to nucleic acid material of a biological sample, thereby forming a hybridization complex and detecting the hybridization complex, wherein the presence of the complex correlates with the presence of km23 nucleic acid forms in the biological sample. Furthermore, a method for the detection of km23 nucleic acid forms is provided herein wherein the method includes the steps of (a) amplifying a km23 nucleic acid form of a biological sample; and (b) detecting sequence alternations in the biological sample. Also included in the present invention is a method for producing a km23 polypeptide, mutant form, or a fragment thereof, the method including culturing a host cell under conditions suitable for the expression of a km23 polypeptide or a fragment thereof and recovering the polypeptide or fragment thereof from the host cell culture. Lastly, a transgenic animal having cells which harbor a transgene encoding a km23 polypeptide, mutant form, or fragment thereof is provided by the present invention. Further provided is a transgenic animal having cells in which a gene for a km23 polypeptide or fragment thereof is disrupted. BRIEF DESCRIPTION OF THE DRAWINGS: Fig. 1. Alignment of human (h) and rat (r) km23 cDNA's, including the 5' and 3' regions. A: The coding region from 1 to 96 is shown with consensus phosphorylation sites for protein kinase C (PKC) and casein kinase II (CKII) designated by brackets above each potential site. Fig. 2. Alignments of various motif regions in km23. Ribosomal Protein S28e (2-25), Dihydroorotate dehydrogenase (16-29), FAD-Dependent Glycerol-3- Phosphate Dehydrogenase (17-33), Pyridine Nucleotide-Disulphide Oxidoreductase (19-31), ATP Citrate Lyase/Succinyl-CoA Ligase (20-30), Ribosomal Protein S19e (56-89), Kringle Domain (61-75). Fig. 3. Alignment of wild-type km23 with sequence alterations found in human ovarian tumor samples. Malignant epithelial cells from ovary tumor samples were laser capture micro-dissected. The coding region was PCR amplified, purified, and sequenced to identify alterations from wild-type sequence. A: Alterations in the oxidoreductase domain from amino acids 22-31 of hkm23. B: Alterations in the PKC/ CKII phosphorylation site from amino acids 55-60. C: Alterations in the Kringle domain from amino acids 64-75. Fig. 4. RI and REE TGFβ receptors are present in km23 immunocomplexes. A: 125 I-TGFβ affinity labeling of 293T cells transiently transfected with km23-flag, RI- myc, and RII-HA After the 4 h 125 I-TGFβ labeling period (4° C), the cross-linking agent disuccinimidylsuberate (DSS) was added for an additional 15 min. Total cell lysates (lanes 1-2), or lysates immunoprecipitated (IP'd) with an anti-flag M2 antibody (Ab) (lanes 3-6) or with IgG (lane 7, control) were visualized by SDS-PAGE. B: Flag immunoblot of cell lysates as in A confirms km23 expression in the relevant lanes (2, 4-6). C: Myc immunoblot of cell lysates demonstrating expression of Rl-myc in the relevant lanes (2, 5-6). D: RII immunoblot of cell lysates demonstrating expression of RII-HA in the relevant lanes (2, 5-6). Fig. 5. km23 is phosphorylated by the RI/RII TGFβ receptor complex. 293T cells were transiently transfected with RI-V5, RII-HA, and either empty vector (EV) or km23-flag. 48h after transfection, cells were labeled for 3h with [ 32 Pi], lysed, and IP'd with an anti-flag Ab. A: In vivo phosphorylation of km23 was visualized by SDS-PAGE and autoradiography. B: Flag immunoblot of A confirms expression of km23-flag in the relevant lanes (2,5). C: V5 immunoblot of A confirms expression of RI-V5 in the relevant lane (5). D: HA immunoblot of A confirms expression of RII- HA in the relevant lane (5). Fig. 6. Kinetics for TGFβ Induction of km23 Expression in MDCK cells. MDCK cells were transiently transfected with km23-flag. 36h after transfection, cells were treated with TGFβ for various time points and then lysed. Total cell lysates were subjected to Western Blot analysis with an anti-flag Ab. Fig. 7. Induction of CRE-Lux luciferase activity by km23 and TGFβ or its receptors. A: 293T cells were transfected with 0.2 ug CRE, 0.05 ug Renilla, and 0. lug of either Rl-flag, RII-HA and km23-flag as indicated. 48 h later, cells were lysed and the Luciferase Assay was performed using the Dual Luciferase Assay System (Promega). The results are representative of triplicate experiments. B: MvlLu cells were transfected with 0.4 ug cis-CRE, 0.08 ug Renilla, and either 0.04, 0.2, or 0.4 ug of km23 or its empty vector as indicated. 21 h later, cells were changed to serum-free conditions for 1 h, followed by treatment with TGFβ (10 ng/ml) for 24 h. The results are representative of triplicate experiments. Fig. 8. Interaction of km23 with dynein in MDCK cells. MDCK cells were transiently transfected with either empty vector or km23-flag. 36h after transfection, cells were treated with TGFβ for various time points and then lysed. Cell lysates were subjected to immunoprecipitation using a monoclonal anti-dynein Ab, followed by immunoblot analysis using an anti-flag Ab (A). Cell lysates were then blotted with anti-flag (B) or anti-dynein (C) as controls for expression. The presence of the km23 bands in lanes 2-5 (A) indicates that dynein and km23 interact in all samples in which km23 was expressed, and that TGFβ increases this interaction (lanes 3-5). Fig. 9. km23 interacts with Smad2 via GST pull-down assay. 293 T cells were transfected with Flag-tagged Smad2 and lysates were incubated with sepharose- bound bacterially expressed GST alone, GST-rkm23, or GST-SBD (Smad-binding domain of SARA, positive control). A: GST- bound proteins were analyzed by SDS- PAGE (10 % ) and were immunoblotted with an anti-flag Ab. Flag-tagged proteins were detected by ECL. Smad 2 interacts with GST-km23 and GST-SBD, but not with GST alone (control). Empty vector (EV) control lanes were also negative. B: Western blot analysis with an anti-Flag Ab to confirm expression of Smad2 in the relevant lanes (2, 4, 6). C: Coomassie staining of gel in A demonstrating the presence of GST and GST fusion proteins in the relevant lanes. The sizes are as expected for the different fusion proteins (approx. 37 kDa for GST-km23, approx. 35 kDa for GST-SBD) or GST alone (approx. 27 kDa). DETAILED DESCRTPTION OF THE INVENTION: The present invention is based on the discovery of the inventor that a protein termed km23 associates with a transforming growth factor β (TGFβ) receptor. The km23 protein, fragments thereof, and the nucleic acid forms encoding them satisfy a need in the art by providing new compositions which are useful in the diagnosis, prevention and treatment of disorders associated with altered expression or activity of the km23 protein. Any means of altering expression or activity of TGFβ signal transducers or modulators, inclusive of km23, via molecular and immuno logical approaches, as well as by using pharmacological agonists or antagonists, will have important consequences for the treatment of cancer and many other human diseases for which TGFβ superfamily members regulate the relevant cellular processes involved. It is noted that unless indicted otherwise, km23 forms include km23 polypeptides, fragments or mutants thereof, polypeptides and fragments which are of the same superfamily as the km23 protein, as well as all relevant nucleotide sequences. Moreover, for purposes of this invention, useful km23 mutants include, but are not limited to, those described herein. The present inventor has used a modification of a cloning of receptors targets (CORT) protocol to identify a protein which interacts with the TGFβ receptor. The original protocol required significant modifications for the application to the identification of TGFβ receptor signaling mediators. Briefly, the phosphorylated, activated intracellular domains of the TGFβ receptor complex were used as a probe, under highly specific conditions, to screen an expression library that was prepared by the inventor from a highly TGFβ resposive intestinal, epithelial cell line from rat. This cell line was developed in the inventor's laboratory. Several positive clones were obtained, one of which was termed km23. The nucleic acid sequence obtained from the km23 rat clone is represented by the formula in SEQ ID NO: 4. The cDNA represented in SEQ ID NO: 4, was found to encode the amino acid sequence represented in SEQ ID NO: 2. Moreover, a further clone of 2.8 kb was isolated from rat and is represented by the formula in SEQ ID NO: 5. The 2.8 kb sequence shown by Seq. ID NO:5 contains km23 sequence within it. A full-length clone was further obtained from a human placental expression library, the sequence for which is represented by the formula in SEQ ID NO: 3. The full-length cDNA from human was found to encode the amino acid sequence represented by SEQ ID NO: 1. It is noted that throughout the specification, km23 is intended to represent all nucleic acid forms with homology to the original km23 clone isolated from rat, as well as polypeptide species and fragments thereof derived from these nucleic acid forms. Referring now to Figure 1, which shows the alignment of the human and rat km23 cDNA, including the 5' and 3' regions, the coding region of the human cDNA is shown as extending from amino acids 1-96 and is shown as having consensus phosphorylation sites for protein kinase C (PKC) and casein kinase II (CKII) as designated by brackets above each potential site. In addition, there are several transcriptional regulatory elements in both the 5' and 3' regions, such as, but not limited to, AP-1, SBE, AP-4, and TCE. The rat and human sequences are 96% identical and 98% similar based on their cDNA sequences. Based upon homology to sequences in the data base, km23 was determined to be part of a new family of dynein-associated proteins which are both Drosophila roadblock-like, (robl), Chlamydomonas dynein light chain (LC)-like, and Drosophila bithoraxoid (bxd)-like (Bowman et al., 1999). Based on a review of the Bowman report, as well as further examination of sequences in available databases, it was determined that km23 is identical to the class 1 mammalian robl-like proteins thought to play a role in cytoplasmic dynein functions. However, no association was ever previously made between the class 1 mammalian robl-like proteins and TGFβ superfamily signaling. The results detailed in the examples shown below demonstrate that km23, in addition to being a member of the dynein-associated proteins, is a TGFβ signaling intermediate. The results detailed in the example section demonstrate that km23 protein interacts with the TGFβ receptors, is phosphorylated by them, and synergizes with TGFβ to stimulate transcriptional activation of a cAMP-responsive element (CRE) reporter. The inventor's results further demonstrate that km23 does, in fact, bind to dynein. The inventor's finding that TGFβ can regulate a member, namely km23, of the dynein-associated proteins, and thereby control dynein motoring along microtubules towards the minus ends, indicates a novel function for TGFβ in microtubule dynamics. A clear role for km23 as a signaling intermediate in the TGFβ signal transduction pathway was established by the following specific findings of the inventor: (1) both the RI and RII TGFβ receptors are present in km23 immuno complexes; (2) km23 is phosphorylated by the RI/RII TGFβ receptor complex; (3) TGFβ is capable of inducing the expression of km23 proteins in MDCK cells, a canine kidney cell type; (4) km23 can synergize with the TGFβ receptor complex and with TGFβ to stimulate CRE luciferase reporter activity, indicating km23 may include as one of its functions the indirect regulation of transcriptional events; (5) km23 interacts with Smad 2, which is an important signaling component of the TGFβ signaling pathway; and (6) km23 inhibits cell growth of MDCK cells. Referring to Figure 3, which shows the alignment of wild-type km23 with sequence alterations found in human ovarian tumor samples, the inventor has further shown that 6 out of 7 (or 86%) ovarian tumor specimens which were laser-capture microdissected samples, displayed km23 mutations in the coding region of the nucleic acid sequence. For example, several alterations were found in the oxido-reductase domain at amino acids 22, 25 and 26 of human km23. Moreover, alterations were found in potential protein kinase C (PKC) or CKII phosphorylation sites at amino acids 57-60. Further alterations were found in the Kringle domain at amino acids 72 and 75; the Kringle domain plays a role in binding membranes, proteins, or phospholipids and can also regulate proteolysis. Any disruption of the Kringle domain of km23 or of other protein domains would be expected to prevent the ability of km23 to act as a signaling intermediate of the TGFβ signaling pathway or could prevent or alter interactions between km23 protein and other signaling components in the TGFβ pathways. Based on its role as a mediator of TGFβ activity and further based on the mutational analysis described above, it is likely that the km23 gene acts as a tumor suppressor gene. In fact, the inventor has preliminary studies showing that the km23 protein encoded by the km23 gene acts as an inhibitor of cell growth. In particular, it has been found that stable expression in MDCK cells of an expression vector carrying the human cDNA sequence for the km23 protein not only resulted in substantial growth inhibition of the cells, relative to the empty vector-transfected control cells, but some of the cell clones stably expressing km23 appear to have undergone either growth arrest or replicative cell senescence. After several weeks in culture, they no longer appear to be dividing and will not proliferate. In addition, a more flattened and elongated morphological appearance is induced by stable expression of km23, as is an increase in actin cables associated with increased cell adhesion. These cellular responses are typical of epithelial cells treated with TGFβ. Phase contrast photographs of the cells stably expressing km23 for three weeks demonstrate that the cells are blocked in cell division. Since TGFβ is present everywhere in the body and regulates a diverse array of cellular functions, a km23 protein or fragment thereof which mediates or modulates TGFβ signals inside the cell is important as a therapeutic target. Any means of altering the expression or activity of km23 family members would have important consequences for TGFβ responses. Accordingly, this invention has applicability related to any need for signal transducers or modulators of TGFβ superfamily members and related uses. Polypeptides According to the present invention there is provided an isolated or recombinant km23 polypeptide, or a functional or mutant analog thereof, in a pharmaceutical composition suitable for humans which mediates or modulates the signal transduction activity of at least one TGFβ superfamily member. In one embodiment, the polypeptide for use in a pharmaceutical composition includes an amino acid sequence represented in the general formula of SEQ ID NO: 1 or fragments thereof. The pharmaceutical composition may further comprise a biocompatible pharmaceutical carrier. This may, in one embodiment, be clinical grade sterile water. However any acceptable biocompatible pharmaceutical carrier may be useful such as, but not limited to, saline, buffered saline and dextrose. As described above, useful km23 polypeptides are those capable of mediating or modulating the signal transduction activity of the growth factor TGFβ and its superfamily members. It is well within the contemplation of the present invention that only a fragment of the km23 protein may be necessary for functional activity. To this end, Figure 2 illustrates various alignments of various motif regions in km23. For example, the region of homology to pyridine nucleotide disulfide oxidoreductase at amino acids 19-31 is of interest since oxido-reductases catalyze oxidation/reduction reactions and could represent a mechanism by which cytoplasmic levels of reducing equivalents could regulate dynein motor activity. As discussed above and in the example section below, the km23 protein is a dynein-associated protein. Moreover, amino acid alterations found in the ovarian tumor cells described above also fall within the oxido-reductase domain, as shown in Fig. 3A. Moreover, some of these amino acid alterations are within a ribosomal protein S28e site located between amino acids 2-25, a dihydroorotate dehydrogenase site from amino acids 16- 29, and an ATP citrate lyase/succinyl-CoA ligase site from amino acids 20-30, further indicating that this region is important for km23 function and its regulation. Further, as described above, amino acid alterations found in tumor cells (Fig. 3B) correspond to a potential site for consensus phosphorylation for both protein kinase C (PKC) and casein kinase II (CKII), located between amino acids 56-59 as shown in Figures 1 and 3B, indicating that this region is important for proper function of the km23 protein. This is particularly true in view of the fact that, as described, km23 is phosphorylated by the TGFβ receptor. Moreover, as described above, the Kringle domain located between residues 61-75 in Figures 2 and 3C is of particular interest since amino acid alterations have been found in ovarian tumor cells in this region and since this domain plays an important role in binding membranes, proteins, or phospholipids and can also regulate proteolysis as described. Finally, amino acid alterations found in the tumor cells of ovarian tissue also fall within a ribosomal protein S19e motif which is located between amino acids 56-89 of a human protein as shown in Figure 2, as well as a nisH/FrxC family motif at amino acids 31-69 of the human km.23 protein (not shown). Furthermore, these motifs directly proceed the Kringle domain in km23 and are potentially important for its function. On the basis of the positioning of various motif regions potentially important for km23's function and regulation and further based on amino acid alternations found in ovarian tumor cells, it is well within the contemplation of the present invention that only a fragment of the km23 protein may be required for functional activity. Therefore, in one embodiment of the present invention, a km23 polypeptide fragment useful in the present invention is of mammal and corresponds to amino acids 1-25 in SEQ ID NO: 1 or SEQ ID NO: 2. In a further embodiment, the fragment may include the amino acids corresponding to amino acids 1-31 in SEQ ID NO: 1 or SEQ ID NO: 2. Further embodiments include fragments corresponding to amino acids 2-96, 16-96, 19-96, 32- 96, 1-47, 1-60, 1-75, 1-89, wherein amino acid numbers correspond to those in SEQ ID NO: 1 or SEQ ID NO: 2. Of note, is the fragment corresponding to amino acids 1-75 in SEQ ID NO: 1 or SEQ ID NO: 2, which fragment corresponds to an isolated mutated km23 protein in a truncated form which results from a premature stop codon. In one embodiment of this invention the km23 protein, mutant protein, or fragments thereof include functional consensus phosphorylation sites. In a further embodiment, the km23 protein, mutant protein, or fragments thereof are capable of stimulating or inhibiting intracellular signal transduction pathways mediated by TGFβ superfamily members. In one desired embodiment, the km23 protein or a mutant protein present in a pharmaceutical composition suitable for humans or a fragment thereof interacts with dynein, wherein the interaction with dynein is modulated by TGFβ superfamily members. It is well within the contemplation of the present invention that proteins which are of the same superfamily as km23 may be used in the pharmaceutical compositions described herein. Furthermore, fragments of proteins which are of the same superfamily as km23 may be useful in the present invention. The present invention further provides mutant km23 polypeptides which alter the function of a growth factor or cytokine signaling pathway. Such mutant km23 polypeptides desirably alter the function of the TGFβ growth factor signaling pathway. In particular embodiments, the mutant km23 polypeptide is a polypeptide which is selected from the following group: (a) a mutant km23 polypeptide having a Met at the amino acid corresponding to amino acid 22 of SEQ ID NO: 1 or SEQ ID NO: 2; (b) a mutant km23 polypeptide having a Lys at the amino acid corresponding to amino acid 25 of SEQ ID NO: 1 or SEQ ID NO: 2; (c) a mutant km23 polypeptide having a Asp at the amino acid corresponding to amino acid number 26 of SEQ ID NO: 1 or SEQ ID NO: 2; (d) a mutant km23 polypeptide having a Met or Ala at the amino acid corresponding to amino acid number 57 of SEQ ID NO: 1 or SEQ ID NO :2; (e) a mutant km23 polypeptide having a Val, His, Asp, or Gly at the amino acid corresponding to amino acid number 58 of SEQ ID NO: 1 or SEQ ID NO: 2; (f) a mutant km23 polypeptide having a Glu or Asn at the amino acid corresponding to amino acid number 59 of SEQ ID NO: 1 or SEQ ID NO: 2; (g) a mutant km23 polypeptide having a Ser at the amino acid corresponding to amino acid number 60 of SEQ ID NO: 1 or SEQ ID NO: 2; (h) a mutant km23 polypeptide having a Cys at the amino acid corresponding to amino acid number 72 of SEQ ID NO: 1 or SEQ ID NO: 2; arid (i) a mutant km23 polypeptide comprising a truncated mutant km23 protein corresponding to amino acid number 1 to amino acid 75 of SEQ ID NO: 1 or SEQ ID NO: 2. (j) a mutant km23 polypeptide having a Leu at the amino acid corresponding to amino acid number 37 of SEQ ID NO: 1 or SEQ ID NO: 2; (k) a mutant km23 polypeptide having a Glu at the amino acid corresponding to amino acid number 41 of SEQ ID NO: 1 or SEQ ID NO: 2; (1) a mutant km23 polypeptide having a Pro at the amino acid corresponding to amino acid number 45 of SEQ ID NO: 1 or SEQ ID NO: 2;(m) a mutant km23 polypeptide having a Leu at the amino acid corresponding to amino acid number 46 of SEQ ID NO: 1 or SEQ ID NO: 2; (n) a mutant km23 polypeptide having a Asn at the amino acid corresponding to amino acid number 44 of SEQ ID NO: 1 or SEQ ID NO: 2; (o) a mutant km23 polypeptide having a Val at the amino acid corresponding to amino acid number 35 of SEQ ID NO: 1 or SEQ ID NO: 2; (p) a mutant km23 polypeptide having a Cys at the amino acid corresponding to amino acid number 42 of SEQ ID NO: 1 or SEQ ID NO: 2; The invention further provides for a fusion protein including a km23 polypeptide, or mutant thereof, and a second polypeptide having an amino acid sequence unrelated to the amino acid sequence of the km23 polypeptide. For example, in one desired embodiment, the second polypeptide functions as a detectable label for detecting the presence of the fusion protein or as a matrix-binding domain for immobilizing the fusion protein. Further encompassed within the present invention is a cloned nucleic acid molecule encoding the fusion protein described above. The invention includes functional equivalents of the km23 protein and its fragments and mutant fragments described herein. Desirably, a protein or fragment is a functional equivalent if its amino acid sequence is at least approximately 60% identical, preferably at least approximately 70% identical. However, the percent identity may be considerably lower than this based on the percent identity of related robl62A (24%), robl37BC (23%) and Drosophila bithoraxoid (bxd) (23%). It is preferred that the km23 protein, mutant protein, or fragments thereof are derived from a mammalian species. Mammals include laboratory animals, such as rats, mice, and rabbits; farm animals, such as cows, pigs, horses and sheep; pet animals, such as dogs and cats; and primates, such as monkeys, orangutans, apes, and humans. The preferred mammals include mice or humans. The km23 protein and protein fragments are preferably isolated. By the term isolated it is meant that the km23 protein or fragments thereof is partially purified or purified to homogeneity. The protein is considered partially purified if it as at least 25%, preferably at least approximately 50%, more preferably at least approximately 75%, most preferably at least approximately 90% and optimally at least approximately 95% free of other proteins. The protein or protein fragment is considered to be purified to homogeneity if it exhibits a single band by SDS page. Cloned Nucleic Acid Molecules The present invention provides for km23 nucleic acid forms which encode the km23 protein, or mutated versions thereof, for use in pharmaceutical compositions suitable for humans. The invention further encompasses nucleic acid forms which encode only a portion of km23 protein or km23 polypeptide, as well as any derivatives thereof. For example, a useful cDNA corresponds to that isolated from human which is shown in the formula of SEQ ID NO: 3. This cDNA includes the entire coding region for the human km23 protein represented in SEQ ID NO: 1. Moreover, any portion of the cDNA sequence of SEQ ID NO: 3 may be useful for production of the protein fragments described herein. In one desired embodiment, the nucleic acid encoding the km23 protein, mutant versions, or fragments thereof includes a 5' or 3' regulatory sequence. Desirably, the regulatory sequence is operably linked to nucleotide sequence encoding a km23 polypeptide or fragment thereof. As described above, the nucleic acid form would desirably encode a km23 polypeptide or fragment which modulates the intracellular signal transduction pathways mediated by TGFβ superfamily members. It is desired that the nucleic acid form is derived from a mammal, preferably a human. In various embodiments, the nucleic acid forms of the present invention encode particular fragments of the km23 protein such as those corresponding to the following amino acids in SEQ ID NO: 1 or SEQ ID NO: 2: 1-25, 1-31, 2-96, 16-96, 19-96, 32-96, 1-47, 1-60, 1-75, 1-89. A further cloned km23 nucleic acid form encompassed by the present invention is shown in the formula of SEQ ID NO: 5. This corresponds to a 2.8 kb polynucleotide which was isolated from rat; the 2.8kb rat form contains km23 sequence within it. It is well within the contemplation of the present invention that mRNA transcribed from this nucleotide sequence provides a regulatory role for km23 and/or TGFβ superfamily members. Moreover, 5' or 3' regulatory sequences present in the DNA sequence may have a further role. Also included within the scope of the present invention are altered nucleic acid sequences encoding km23 polypeptide or a fragment thereof. Such alterations may include, but are not limited to, deletions, insertions, or substitutions of different nucleotides resulting in a nucleic acid form that encodes the same or a functionally equivalent km23 protein. To this end, the encoded protein may also contain deletions, insertions, or substitutions of amino acid residues which produce a silent change and results in a functionally equivalent km23 protein. Such altered nucleic acid sequences and their encoded proteins may be useful for therapeutic purposes. This aspect of the present invention is further described below. Also included within the scope of the invention are altered nucleic acid sequences resulting from at least one mutation in a nucleic acid ' sequence, which altered nucleic acid sequences may result in a polypeptide whose structure or function is altered. Such altered nucleic acid forms and the polypeptides resulting from them may be useful in the area of diagnosis of a particular disorder or design of therapeutic agents against such a disorder. This is further described below. In one embodiment, a cloned mutant km23 nucleic acid form, which functions in a growth factor or cytokine signaling pathway, is a mutant characterized by a mutation of at least one nucleotide base relative to a wild-type km23 nucleic acid form, which mutation results in a mutant km23 polypeptide selected from the group of mutant km23 polypeptides having the following amino acid changes, which correspond to the amino acid number in SEQ ID NO: 1 or SEQ ID NO: 2: (a) a mutant km23 polypeptide having a Met at amino acid no. 22; (b) a mutant km23 polypeptide having a Lys at amino acid no. 25; (c) a mutant km23 polypeptide having a Asp at the amino acid corresponding to amino acid no. 26; (d) a mutant km23 polypeptide having a Met or Ala at the amino acid corresponding to amino acid no. 57; (e) a mutant km23 polypeptide having a Val, His, Asp, or Gly at the amino acid corresponding to amino acid no. 58; (f) a mutant km23 polypeptide having a Glu at the amino acid corresponding to amino acid no. 59; (g) a mutant km23 polypeptide having a Ser at the amino acid corresponding to amino acid no. 60; (h) a mutant km23 polypeptide having a Cys at the amino acid corresponding to amino acid no. 72; and (i) a mutant km23 polypeptide which is a truncated mutant km23 protein conesponding to amino acid no. 1 to amino acid no. 75; (j) a mutant km23 polypeptide having a Leu at the amino acid corresponding to amino acid number 37 of SEQ ID NO: 1 or SEQ ID NO: 2; (k) a mutant km23 polypeptide having a Glu at the amino acid corresponding to amino acid number 41 of SEQ ID NO: 1 or SEQ ID NO: 2; (1) a mutant km23 polypeptide having a Pro at the amino acid corresponding to amino acid number 45 of SEQ ID NO: 1 or SEQ ID NO: 2; (m) a mutant km23 polypeptide having a Leu at the amino acid conesponding to amino acid number 46 of SEQ ID NO: 1 or SEQ ID NO: 2; (n) a mutant km23 polypeptide having a Asn at the amino acid corresponding to amino acid number 44 of SEQ ID NO: 1 or SEQ ID NO: 2; (o) a mutant km23 polypeptide having a Val at the amino acid corresponding to amino acid number 35 of SEQ ID NO: 1 or SEQ ID NO: 2; (p) a mutant km23 polypeptide having a Cys at the amino acid conesponding to amino acid number 42 of SEQ ID NO: 1 or SEQ ID NO: 2; It is noted that nucleic acid forms encompassed by this invention include, but are not limited to, all functional equivalents of any of the sequences described above. For example, a nucleic acid form would be a functional equivalent if its nucleic acid sequence is at least approximately 60% identical, preferably at least approximately 70% identical; most preferably at least approximately 80% identical, especially preferably at least approximately 90% identical, optimally at least approximately 95% identical, and especially optimally at least approximately 98% identical. Percent identity between the two strands of sequences is calculated by juxtaposing the two strands so as to achieve the highest possible identity of residues. Software is available to aid in the alignment. Preparing km23 Protein and Fragments Thereof The km23 protein of the invention, a mutated version or fragments thereof and DNA encoding the same may be chemically synthesized by methods known in the art. Suitable methods for synthesizing polypeptides are described by Stuart and Young in "Solid Phase Peptide Synthesis," Second Edition, Pierce Chemical Company (1984), Solid Phase Peptide Synthesis, Methods Enzymol., 289, Academic Press, Inc, New York (1997) . Suitable methods for synthesizing DNA are described by Caruthers in Science 230:281-285 (1985) and DNA Structure, Part A: Synthesis and Physical Analysis of DNA, Lilley, D.M. J. and Dahlberg, J.E. (Eds.), Methods Enzymol., 211, Academic Press, Inc., New York (1992). The subject matter of all of the aforementioned citations are incorporated herein by reference. Polypeptides may also be prepared by providing DNA that encodes the protein fragment; amplifying or cloning the DNA in a suitable host; expressing the DNA in a suitable host; and harvesting the protein. For example, the km23 protein or a fragment thereof may be translated either directly or indirectly from a cDNA encoding km23 amino acid sequence. The DNA encoding polypeptides of the invention may be replicated and used to express recombinant protein following insertion into a wide variety of host cells in a wide variety of cloning vectors. Cloning vectors may comprise segments of chromosomal, non-chromosomal, and synthetic DNA sequences. Some suitable prokaryotic cloning vectors include plasmids from£. coli, such as col El, pCR 1, pBR 322, pMB9, pUC, pKSM, and RP4. Prokaryotic vectors also include derivatives of phage DNA such as M13 fd and other filamentous single-stranded DNA phages. The host may be prokaryotic or eukaryotic. The DNA may be obtained from natural sources and, optionally, modified by, for example, site-specific mutagenesis. The genes may also be synthesized from the individual nucleotides in whole or in part. Synthetic methods, such as solid phase methods, are known in the art, such as those described by Caruthers in Science v. 230, pp 281-285 (1985) and DNA Structure Part A: Synthesis and Physical Analysis of DNA, Lilley, D.M. J. and Dahlberg, J.E. (Eds.), Methods Enzymol, v. 211, Academic Press, NY (1992). The invention provides for an expression vector capable of expressing in a host cell a km23 protein, mutant protein, or a fragment thereof such as described above. Vectors for expressing proteins in bacteria, especially E. coli, are also known. Such vectors include the pK 233 (or any of the tac family of plasmids), T7, pBluescript π, bacteriophage lambda, ZAP, and lambda P L (Wu. R. (Ed.). Recombinant DNA Methodology IT Methods in Enzymol.. Academic Press. Inc.. NY. (1995). Examples of vectors with expressed fusion proteins are PATH vectors described by Dieckmann and Tzagoloff in J. Biol. Chem., vol. 260, 1513-1520 (1985). These vectors contain DNA sequences that encode anthranilate synthetase (TrpE) followed by a poly-linker at the carboxy terminus. Other expression vector systems are based on beta-galactosidase (pEX); maltose binding protein (pMAL); glutathione-S-tranferase (pGST or pGEX) - see Smith, D.B. Methods Mol. Cell Biol., vol. 4: pp 220-229 (1993); Smith, D.B. and Johnson, K.S., Gene, vol. 67, pp 31-40 (1988); and Peptide Res., vol. 3; 167 (1990), and TRX (thioredoxin) Fusion Protein (TRX FUS) - see La Vallie, R. et al., Bio/Technology, vol. 11, pp 187-193 (1993). Vectors useful for cloning and expression in yeast are available. Suitable examples are 2μm circle plasmid, Ycp50, Yep24, Yrp7, Yip5, and pYAC3 (Ausubel, F.M. et al. (Eds.), Current Protocols in Molecular Biology, John Wiley & Sons, Inc., New York , (1999)). Suitable cloning/expression vectors for use in mammalian cells are also known. Such vectors include well-known derivatives of SV-40, adenovirus, cytomegalovirus (CMV) retrovirus-derived DNA sequences. Any such vectors, when coupled with vectors derived from a combination of plasmids and phage DNA, i.e. shuttle vectors, allow for the isolation and identification of protein coding sequences in prokaryotes. Further eukaryotic expression vectors are known in the art (e.g., P.J. Southern and P. Berg, J. Mol. Appl. Genet. 1:327-341 (1982); S. Subramani et al, Mol. Cell. Biol. 1:854-864 (1981); R.J. Kaufmann and P.A Sharp, "Amplification And Expression Of Sequences Cotransfected with A Modular Dihydrofolate Reductase Complementary DNA Gene," J. Mol. Biol. 159:601-621 (1982); R.J. Kaufmann and P.A. Sharp, Mol. Cell. Biol. 159:601-664 (1982); S.I. Scahill et al, "Expression And Characterization Of The Product Of A Human Immune Interferon DNA Gene In Chinese Hamster Ovary Cells," Proc. Natl. Acad. Sci. USA 80:4654-4659 (1983); G. Urlaub and L.A. Chasin, Proc. Natl. Acad. Sci. USA 77:4216-4220 (1980). It is noted that expression and cloning vectors will likely contain a selectable marker, a gene encoding a protein necessary for survival or growth of a host cell transformed with the vector. The presence of this gene insures growth of only those host cells which express the insert. Typical selection genes encode proteins that: (a) confer resistance to antibiotics or other toxic substances (e.g. ampicillan, neomyicin, methotrexate, etc.); (b) compliment auxotrophec deficiencies or (c) supply critical nutrients not available from complex media, e.g. gene encoding d-alanine, racenase for Basillia. The choice of the proper selectable marker will depend on the host cell, and appropriate markers for different hosts are well known in the art. The expression vectors useful in the present invention contain at least one expression control sequence that is operatively linked to the DNA sequence or fragment to be expressed. The control sequence is inserted in the vector in order to control and to regulate the expression of the cloned DNA sequence. Examples of useful expression control sequences are ' the lac system, the trp system, the tac system, the trc system, the tet system, major operator and promoter regions of phage lambda, the control region of fd coat protein, the glycolytic promoters of yeast, e.g., the promoter for 3- phosphoglycerate kinase, the promoters of yeast acid phosphatase, e.g., Pho5, the promoters of the yeast alpha-mating factors, and promoters derived from polyoma, adenovirus, retrovirus, and simian virus, e.g., the early and late promoters or SV40, and other sequences known to control the expression of genes of prokaryotic or eukaryotic cells and their viruses or combinations thereof. Once the gene is cloned into such an expression vector, the gene product may be produced in a suitable expression host in either a constitutive or inducible manner. Useful expression hosts include well-known prokaryotic and eukaryotic cells. Some suitable prokaryotic hosts include, for example, E. coli. such as E. coli SG-936, E. coli HB 101, E. coli W3110, E. coli X1776, E. coli X2282, E. coli DH1, E. coli DH5αF', and E. coli MRC1, Pseudomonas. Bacillus, such as Bacillus subtilis. and Streptomyces. Suitable eukaryotic cells include yeasts and other fungi, insect, animal cells, such as COS cells and CHO cells, human cells and plant cells in tissue culture. The invention provides for a host cell transfected with the expression vector of the present invention, which host cell is capable of expressing a km23 polypeptide, or a fragment thereof desirably in a functional form or mutant form. Host cells which contain the nucleic acid sequence encoding km23 and express km23 may be identified by a variety of procedures known to those skilled in the art. These procedures include, but are not limited to, DNA-DNA or DNA-RNA hybridization and protein bioassay or immunoassay techniques which include membrane and solution based technologies for the detection and/or quantification of nucleic acid or proteins. The invention further provides a method for producing a km23 polypeptide or fragment or mutant thereof. The method including: (a) culturing the host cell described above under conditions suitable for the expression of the polypeptide or fragment thereof; and (b) recovering the polypeptide or fragment thereof from the host cell culture. To this end, it is noted that although km23 protein has been found to be a cytoplasmic protein, expression vectors may include secretion signals where appropriate which allow the protein to cross and/or lodge in cell membrane or to be secreted from the cell. Such secretion would facilitate recovery of the polypeptide or fragment thereof from the host cell culture. Such vectors containing secretion signals may be prepared by means as standard recombinant techniques well known in the art and discussed, for example, in Sambrook et al, 1989 or Ausubel et al., 1992. The polypeptides may be purified using standard known techniques. Some examples of suitable techniques include, for example, gel purification, column chromatography, or electrophoretic methods. Recombinant constructions may be used to join sequences encoding km23 to nucleic acid sequence encoding a polypeptide domain which will facilitate purification of soluble proteins. Such purification facilitating domains include, but are not limited to, metal chelating peptides such as histidine-tryptophan modules that allow purification on immobilized metals, protein A domains that allow purification or immobilized immunoglobulin, and the domain utilized in the flags-extension/affinity purification system (Immunex Corp., Seattle, WA). Moreover, signal sequences may be used to facilitate the export of km23 into a cell culture supernatant to facilitate purification of the protein. As described above, the expression vector according to this invention allows for the translation of protein domains which are capable of facilitating the function of km23 to affect various cellular processes associated with the TGFβ signaling pathway, including, but not limited to, inhibiting cellular proliferation. In one embodiment of the present invention, the km23 polypeptide which is expressed is capable of modulating intracellular signal transduction pathways mediated by TGFβ superfamily members. In a particular embodiment of the expression vector, the km23 polypeptide, or mutant version thereof, expressed is capable of modulating at least one of the group including regulation of gene expression, cell growth, cell differentiation, cell survival, apoptosis, senescence, cell migration, angiogenesis, fibrosis, wound healing, extracellular matrix induction, adhesion, autoproduction, embryogenesis and combinations thereof. As described above, km23 protein mediates TGFβ signals inside the cell. This is clearly illustrated in the examples below. To this end, since TGFβ is found everywhere in the body and regulates a diverse array of cellular functions, including those described, any means of altering the expression or activity of km23 or km23 functional analogs has important consequences for TGFβ responses. Thus, transfecting a cell with an expression vector carrying a functional km23 polypeptide affects TGFβ responses. This is further discussed below. In a further embodiment of the present invention, an expression vector according to this invention, which expresses a functional km23 polypeptide or functional equivalent thereof, or a mutant form of km23, is capable of modulates at least one of the group consisting of actin cytoskeleton dynamics, microtubule dynamics, intracellular transport, cell polarity, dynein-mediated microtubule transport and combinations thereof. As illustrated by Example 10 shown below, km23 has been shown to interact with dynein in MDCK cells, which are a type of canine kidney cell type. Based on this association, km23 polypeptides are expected to have an effect on any one of actin cytoskeleton dynamics, microtubule dynamics, intracellular transport, cell polarity, dynein-mediated microtubule transport and combinations thereof. For example, dynein' s role in these various functions have been previously established by others (see for example Hirokawa, 1998). As described above, dynein is a molecular motor protein which mediates intracellular transport; it conveys its cargo along polarized microtubules towards the minus ends. Dynein appears to control various cell functions which include axonal transport, flagellar motility, organization of the mitotic spindle, distribution of late endosomes and lysosomes, the centrosomal localization of the Golgi complex, vesicular transport from early to late endosomes, the apical transport of Golgi-derived membranes in intestinal epithelial cells, the movement of phagosomes, and others as reviewed in Hirokawa, 1998. The inventor's finding that TGFβ can regulate km23 protein, a member of the dynein-associated proteins, and thereby control dynein motoring along microtubules towards the minus ends, demonstrates a novel function for TGFβ in microtubule dynamics. Microtubules are polar structures with a fast-growing plus end and a minus end. They function as "rails" for the transport of organelles via microtubule-associated motor proteins such as dynein. Microtubules are important for many cellular processes, and play an important role in the generation and maintenance of epithelial cell polarity (Hofer et al., 1998). The inventor has established that km23 plays a role in dynein functions in polarized epithelial cells, such as the Madin-Darby canine kidney (MDCK) cells as shown below in the examples and as illustrated in Figure 8. Oligonucleotides and Primers In yet another aspect of the present invention, a substantially pure oligonucleotide or primer is provided, wherein the oligonucleotide or primer includes a region of nucleotide sequence capable of hybridizing under stringent conditions to at least about 12 consecutive nucleotides of sense or anti-sense sequence of the nucleic acid form represented by the formula in SEQ ID NO: 3, SEQ ID NO: 4. In a further embodiment, a substantially pure oligonucleotide or primer is provided wherein the oligonucleotide or primer is provided wherein the oligonucleotide or primer includes a region of nucleotide sequence capable of hybridizing under stringent conditions to at least about 12 consecutive nucleotides of sense or anti- sense sequence of a nucleic acid form represented by SEQ ID NO: 5. Finally, there is provided a substantially pure oligonucleotide or primer, wherein the oligonucleotide or primer includes a region of nucleotide sequence capable of hybridizing under stringent conditions to at least about 12 consecutive nucleotides of sense or anti-sense sequence of any one of the mutant nucleic acid forms described herein. Also encompassed by the present invention are oligonucleotides or primers such as those described above wherein the oligonucleotide or primer further includes a detectable label attached thereto. There is no upper limit to the length of the oligonucleotide probes or primers. However, normally, the oligonucleotide probe will not contain more than 50 nucleotides, preferably not more than 40 nucleotides, and more preferably not more than 30 nucleotides. The oligonucleotides and primers provided by the present invention may be useful for diagnosing a particular disorder, such as by PCR amplification of portions of the km23 nucleotide sequence which may harbor a mutation, insertion, or deletion of a nucleotide base, as one example. Moreover, the probe and primers provided herein may be used as part of anti-sense therapy. This is further described below and relates to a potential therapeutic use of such oligonucleotides or primers. Method of Modulating Intracellular Signal Transduction Pathways Mediated by TGFβ A method of modulating signal transduction pathways mediated by the TGFβ superfamily members is provided by the present invention, wherein the method includes introducing into the cell a km23 polypeptide or functional analog thereof. In one embodiment of this method, the km23 polypeptide is introduced into the cell by expressing in the cell a nucleic acid molecule that encodes km23 polypeptide. Alternatively, the km23 polypeptide may be introduced into the cell by contacting the cell with the polypeptide or a nucleic acid form encoding the polypeptide. Active km23 molecules can be introduced into cells by micro-injection or by use of liposomes, for example, alternatively, some active molecules may be taken up by cells, actively or by diffusion. Extracellular application of the km23 polypeptide can, in this instance, be sufficient to effect cell growth. Desirably, the km23 polypeptide for use in the method described above is of a mammal and most desirably is of a human. In one desired embodiment, the polypeptide includes approximately amino acids 1 to the C-terminus. For example, one useful polypeptide would be the human km23 protein represented in SEQ ID NO: 1. A further useful polypeptide would be that represented by SEQ ID NO: 2. The method above further encompasses the use of a km23 protein fragment. Desirably, the fragment would be capable of facilitating the normal functions of km23 within the cell. Based on the various motifs found in the amino acid sequence for the km23 protein shown in Figure 2, which are relevant to the proper functioning of the protein within the cell, or an analog thereof, as well as positions of various mutations found in ovary tumor cells. Fragments of the protein which may be useful in the method described above include the following peptide fragments, wherein the numbering corresponds to the amino acid sequence shown in SEQ ID NO: 1 or SEQ ID NO: 2: 1-25, 1-31, 2-96, 16-96, 19-96, 32-96, 1-47, 1-60, 1- 75 and 1-89. As described above, the experimental results incorporated herein support the role of km23 protein as an inhibitor of cell growth. Therefore, in one desired embodiment, the cell into which the km23 polypeptide or a functional analog thereof is introduced is a malignant cell. In one embodiment, the cell is a carcinoma. In another embodiment, the cell is an osteocarcinoma, sarcoma, osteosarcoma, glioma, melanoma, myxoma, adenoma, rhabdomyoma-derived cell, or pre-malignant versions thereof. Moreover, the cell may be a lung, breast, colon, prostate, kidney, ovary, liver, testes, skin, heart, pancreas, thyroid, adrenal, pituitary, brain, muscle, uterine or bone cell. The cell may be a metastasized cell. Moreover, the cell may be either a post-embryonic cell or an embryonic cell. The invention further provides a method of modulating intracellular signal transduction pathways mediated by TGFβ superfamily members, wherein the method includes introducing into the cell an agonist of a km23 nucleic acid form or an agonist of amino acids encoded by the nucleic acid form. The present invention further encompasses a method of modulating the intracellular signal transduction pathways mediated by TGFβ superfamily members, the method including introducing into the cell an antagonist of a km23 nucleic acid form, inclusive of mutant forms, or an antagonist of amino acids encoded by the nucleic acid form. Antagonists of both nucleic acid and protein forms of km23 provide a means by which this TGFβ signaling intermediate may be controlled both at a nucleic acid and protein level. In one embodiment, the antagonist of the km23 nucleic acid form is an anti-sense construct. In a further embodiment, the antagonist of the km23 nucleic acid form is a peptide antagonist. For example, the peptide antagonist can effect a change in the cellular localization of the km23 protein. Moreover, antagonists of amino acids encoded by the km23 nucleic acid form include a dominant negative version of the km23 protein or a hormone-inducible or drug-inducible version thereof. In one example, tumor tissue such as ovarian tumor tissue is injected with DNA or RNA, such as mRNA, which, when translated, forms an inactive version of the km23 protein capable of blocking the ability of km23 wild-type protein to mediate TGFβ signal transduction activity. Given the inventor's preliminary data suggesting that km23 is a potent inhibitor of cell growth, translation of a dominate negative version of the km23 protein would be expected to block the ability of TGFβ to inhibit the growth of the cells. If this occurs in cancer patients that express the truncated form of km23 in their cells, then the expressed mutant dominate-negative form can be used as a screen to identify therapeutics for such patients. In a further embodiment, the antagonists of amino acids encoded by the km23 nucleic acid form is a monoclonal antibody. The monoclonal antibody provided herein is further described below. Antibodies This invention provides antibodies, preferably monoclonal antibodies that bind specifically to an antigenic determinant in a km23 polypeptide. In one embodiment, the antigenic determinant to which the monoclonal antibody binds is located within a protein domain responsible for the protein's normal functions. As described above, the antibodies are preferably monoclonal, but may also be polyclonal. Monoclonal antibodies may be produced by methods known in the art. These methods include the immunological method described by Kohler and Millstein in Nature vol. 256, pp 495-497 (1975) and by Campbell in "Monoclonal Antibody Technology", The Production And Characterization Of Rodent And Human Hybridomas" in Burdon, et al. (Eds.), Laboratory Techniques in Biochemistry and Molecular Biology, vol. 13, Elsevier Science Publishers, Amsterdam (1985); and Coligan, J.E., et al. (Eds.), Current Protocols In Immunology, Wiley Intersciences, NY, (1999); as well as recombinant DNA methods described by Huse, et al., Science, vol. 246, pp 1275-1281 (1989). The recombinant DNA method preferably comprises screening phage libraries for human antibody fragments. In order to produce monoclonal antibodies, a host mammal is inoculated with a km23 peptide or peptide fragment as described above, and then boosted. Spleens are collected from inoculated mammals a few days after the final boost. Cell suspensions from the spleens are fused with a tumor cell in accordance with the general method described by Kohler and Millstein in Nature, vol. 256, pp 495-497 (1975). If the fragment is too short to be immunogenic, it may be conjugated to a carrier molecular. Some suitable carrier molecules include key hold limpet, hemocyanin and bovine serum albumin. Conjugation may be carried out by methods known in the art (Coligan, J.E., et al. (Eds.), Current Protocols In Immunology, Chapter 9, Wiley Intersciences, NY, (1999). One such method is to combine a cysteine residue of the fragment with a cysteine residue on the carrier molecule. Methods of Use: Gene Therapy As described above, PCR analysis of human ovarian tumor specimens indicates that mutations of km23 nucleic acid forms are associated with disorders of cell proliferation, and in particular, cancer. Accordingly, the present invention encompasses a method of supplying a wild-type km23 nucleic acid form or a functional analog thereof to a cell which carries a mutated form of a gene. For example, a km23 gene or part of the gene may be introduced into the cell in a vector such that the gene remains extrachromosomal. More preferred, is a situation where the wild-type km23 gene or a part thereof is introduced into the mutant cell in such a way that it recombines with the endogenous mutant km23 gene present in the cell. Methods for introducing DNA into cells such as elecfroporation, calcium phosphate coprecipitation and viral transduction are known in the art. Cells transformed with the wild-type km23 gene can be used as model systems to study cancer remission and drug treatments which promote such remission. As generally discussed above, the km23 gene or fragment, where applicable, may be employed in gene therapy methods in order to increase the amount of the expression products of such genes and cancer cells. Such gene therapy may be particularly appropriate for use in both cancers and pre-cancer cells in which the level of a functional km23 polypeptide is absent or diminished compared to normal cells. Gene therapy is carried out according to generally accepted methods, for example, as described by Friedman in Therapy for Genetic Disease, T. Friedman, Ed., Oxford University Press 1991, pp 105-121. Briefly, cells from a patient's tumor are first analyzed to decipher the production of km23 polypeptide in the tumor cells. A virus or plasmid vector containing a copy of the km23 gene brings to expression control elements incapable of replicating inside the tumor cells is prepared. Suitable vectors include those disclosed in U.S. Patent No. 5,252,479 as well as PCT Published Application WO 93/07282, the subject matter of which are incorporated herein by reference. The vector is injected into the patient, either locally at the site of the tumor or systemically. Anti-sense polynucleotide sequences are useful to modulate km23 activity or to achieve regulation of gene function. To this end, anti-sense to nucleic acid sequence encoding km.23 may be used in situations in which it would be desirable to block the transcription of the mRNA. In particular, cells may be transformed with sequences complimentary to nucleic acid sequences encoding km23. Such technology is now well known in the art, and sense or anti-sense oligomers or larger fragments, can be designed for various locations along the coding or control regions of sequences encoding km23. Methods of Use: Peptide Therapy Peptides, inclusive of polypeptides which have km23 activity can be supplied to cells which carry a mutated km23 gene. The sequence of the km23 protein of human is disclosed in SEQ ID NO: 1. Protein can be produced by expression of cDNA sequence in bacteria, for example, using known expression vectors described above. Alternatively, km23 polypeptide can be extracted from km23 -producing mammalian cells. Moreover, the techniques of synthetic chemistry can be employed to synthesize km23 protein. Any of such techniques can provide the preparation of the present invention which includes the km23 protein. The preparation is substantially free of other human proteins. This can be most readily accomplished by synthesis of the protein in a micro-organism or in vitro. The preparation is a pharmaceutical composition. The pharmaceutical composition including the km23 protein or peptide may be administered in conjunction with a pharmaceutically acceptable carrier, such as clinical grade sterile water. Moreover, such compositions may, in addition to including km23 derivatives, further include agonists or mimetics of km23. The pharmaceutical compositions utilized in this invention may be administered by any number of routes including, but not limited to, oral, intravenous, intra-muscular, intra-arterial, intra- medullary, intra-thecal, intra-ventricular, transdermal, subcutaneous, intra-peritoneal, intra-nasal, enteral, topical, sublingual, or rectal means. Active km23 polypeptides or derivatives thereof can be introduced into cells by microinjection or by use of liposomes, for example. Alternatively, some active molecules may be taken up by cells actively or by diffusion. It is noted that any of the therapeutic proteins, antagonists, antibodies, agonists, anti-sense sequences or vectors described above may be administered in combination with other appropriate therapeutic agents. Selection of the appropriate agents for use in combination therapy may be made by one of ordinary skill in the art. This combination of therapeutic agents may act in a synergistic manner to effect the treatment or prevention of the various disorders described above. Using this approach, therapeutic efficacy with lower doses of each agent may be achieved, thus reducing the potential for adverse side effects. Methods of Use: Diagnostics The present invention provides for a method of determining if a patient is at risk for a disorder or has a disorder, the method including detecting in a patient's specimen the presence or absence of a lesion characterized by an alteration in sequence, expression, post-translational modification, or some combination thereof of km23 nucleic acid or polypeptide forms. In one embodiment of the method of determining if a patient is at risk for a disorder or has a disorder, the presence or absence of a lesion is characterized by: (a) a mutation of the gene encoding a km23 polypeptide or a homologue thereof; (b) a mis-expression of the gene; (c) an altered signal transduction activity of the polypeptide and combinations thereof. For example, in one embodiment, antibodies which specifically bind km23 proteins may be used for a diagnosis of conditions or diseases characterized by expression or modification of a km23 protein. Alternatively, such antibodies may be used in assays to monitor patients being treated with a functional km23 protein or its analogs, agonists, antagonists or inhibitors. The antibodies used for diagnostic purposes may be prepared in the same manner as those described above for therapeutics. Diagnostic assays for km23 protein include methods which utilize a labeled antibody to detect km23 protein in human body fluids or extracts of cells or tissues. The antibodies may be used with or without modification, and may be labeled by joining them with a reporter molecule. Such reporter molecules are known in the art. Various protocols including ELISA and FACS for measuring km23 protein levels are known in the art and provide a basis for diagnosing altered or abnormal levels of km23 expressions. Normal or standard values for km23 expression may be established by combining body fluids or cell extracts from normal mammalian subjects, such as human, with antibodies to km23 protein under conditions suitable to form a complex. Furthermore, functional assays can be used in the diagnosis of a particular disorder. For example, it is known that km23 protein is a protein capable of associating with the TGFβ receptor complex. Thus, an assay to assess the ability of a particular km23 protein form to associate with the receptor can be employed in the determination of whether a patient has a particular disorder. In a further embodiment of the invention, polynucleotides encoding km23 amino acid sequence or mutant versions may be used for diagnostic purposes. These polynucleotides may include oligonucleotide sequence such as anti-sense, RNA and DNA molecules. For example, polynucleotides may be used to detect and quantitate gene expression in biopsied tissues in which expression of km23 may be correlated with a disease. The diagnostic assay can be used for example to distinguish between the absence, presence , or an excess expression of km23 as well as to monitor the regulation of km23 levels during therapeutic intervention. It is also contemplated within the scope of the invention that the nucleic acid probe assays will employ a cocktail of nucleic acid probes capable of detecting km23 genes. A wide variety of labels and conjugation techniques are known by those skilled in the art and may be used, for example, in the various nucleic acid hybridization assays and amino assays. Methods for producing labeled hybridization or PCR probes for detecting sequences related to polynucleotides encoding km23 include oligo-labeling, mixed translation, and labeling or PCR amplification using a labeled nucleotide. Suitable labeled reporter molecules which may be used include radio nuclides, enzymes, fluorescents, chemiluminescent, or chromogenic agents as well as substrates, cofactors, inhibitors, magnetic particles, and the like. In one aspect of the invention, DNA sequences of the km23 gene which have been amplified by use of PCR may be screened using mutation-specific probes. For example, these probes are nucleic acid oligomers, each of which contains a region of a km23 gene sequence harboring a known mutation. By use of a battery of such mutation-specific probes, PCR amplification products can be screened to identify the presence of a previously identified mutation in the km23 gene. Such hybridization of mutation-specific probes with amplified km23 nucleic acid sequences can be performed, for example, on a nylon filter. Hybridization to a particular probe under stringent hybridization conditions would indicate the presence of the same mutation in the tumor tissue as in the mutation-specific probe. In a related aspect, hybridization with PCR probes which are specific for the wild-type sequence may be used to identify mutations in the wild-type sequence. The ability of the probe to identify naturally occurring sequences encoding km23, mutations, or related sequences, will depend on the stringency of the hybridization or amplification. Probes used for the detection of km23 -related sequences should preferably contain at least 50% of the nucleotides from any of the km23 encoding sequences. The hybridization probes of the invention may be DNA or RNA and are preferably derived from the nucleotide sequence of SEQ ID NO: 3 corresponding to cDNA encoding human km23 protein or from genomic sequence including promoter, enhancer elements, and introns of the naturally occurring km23 nucleic acid form. Additional diagnostic uses for oligonucleotides designed from the sequences encoding km23 protein may involve the use of PCR. Such oligomers may be chemically synthesized by methods described above. Moreover, such oligonucleotides may be generated enzymatically or produced from a recombinant source. Oligomers will preferably consist of two nucleotide sequences, one with sense orientation and another with anti-sense orientation, employed under optimized conditions for identification of a specific gene or condition. The specific oligomers or, alternatively, a degenerate pool of oligomers may be employed under less stringent conditions for the detection and/or quantitation of closely related DNA or RNA sequences. In a particular aspect, primer pairs of the present invention are useful for determination of the nucleotide sequence of a particular mutated form of km23 gene using PCR. The pairs of single-stranded DNA primers can be annealed to sequences within or surrounding the km23 gene in order to amplify DNA sequence of the km23 gene itself. A complete set of these primers allows synthesis of all of the nucleotides of the km23 gene coding sequences, that is, the exons. The set of primers preferably allows synthesis of both intron and exon sequences. Mutation-specific primers can also be used, wherein such primers anneal only to particular km23 mutant genes, and thus will only amplify a product in the presence of the mutant gene as a template. Alternation of km23 mRNA expressions can be detected by any techniques known in the art. These include Northern blot analysis, PCR amplification, as well as Rnase protection. Diminished mRNA expression indicates an alteration of the wildtype km23 gene. Alteration of the wild-type km23 gene can also be detected by screening for alteration of wild-type km23 protein. For example, as described above, antibodies such as monoclonal antibodies immunoreactive with km 23 can be used to screen a tissue. Lack of cognate antigen would indicate a km23 mutation. Antibodies specific for products of mutant km23 genes could also be used to detect a mutant km23 gene product. Such immunological assays can be done in any convenient format known in the art. These include Western blot, immunoblots, chemical assays and ELISA. Methods for Identifying Therapeutic Agents The present invention provides a method for identifying therapeutic agents that inhibit, potentiate, or mimic the ability of a km23 polypeptide or a nucleic acid encoding the polypeptide to modulate the signal transduction activity of a TGFβ growth factor, the method including: treating a cell with an effective amount of at least one candidate so as to alter at least one of regulation of gene expression, cell growth, cell differentiation, cell survival, apoptosis, senescence, cell migration, antiogenesis, fibrosis, wound healing, extra cellular matrix induction, adhesion, auto production, embryogenesis and combinations thereof; and (b) measuring the effect of the candidate on the cell. In one embodiment candidates which are therapeutic agents that modulate or mediate at least one of the cellular functions described above do so by an amount at least 10%) relative to the cell in the absence of the candidates. In a particular embodiment, a method for identifying therapeutic agents that inhibit the proliferation of the cell is provided, the method including measuring the effect of a candidate on the proliferation of the cell, wherein candidates that inhibit the proliferation of the cell by an amount at least 10% that of a functional km23 polypeptide are therapeutic agents. In one embodiment, the therapeutic agent inhibits the proliferation of the cell by an amount at least about 25% that of the functional km23 polypeptide. In a further embodiment, the therapeutic agent inhibits the proliferation of the cell by an amount at least about 50% that of the functional km23 polypeptide. In a further embodiment, the therapeutic agent inhibits the proliferation of the cell by an amount at least about 75% that of the functional km23 polypeptide. Most desirably, the therapeutic agent would inhibit the proliferation of the cell by an amount at least about 90% that of the functional km23 polypeptide. It is noted that the proliferation may be inhibited either ex vivo or in vivo. In this method, therapeutic candidates are compared in performance with a standard, wherein the standard is a functional km23 polyeptide. In one aspect of the invention, km23, its catalytic or immunogenic fragments, or mutant fragments or forms, or oligo peptides thereof, can be used for screening libraries of compounds using any of a variety of drug screening techniques. The fragment employed in such a screening may be free in solution, affixed to a solid support, borne on a cell surface, or located intracellularly. The formation of binding complexes between km23 and the agent being tested, may be measured. Formation of a complex between km23 and an agonist agent would have the effect of potentiating the ability of km23 to act as a signaling intermediate in the TGFβ signaling pathway. Alternatively, the formation of a binding complex between km23 and an antagonist of its function can inhibit its ability to act as a signaling intermediate in the TGFβ pathway and can provide an overall means of modulating km23 activity. This latter effect may be useful for application to cells other than the tumor epithelial cells in an in vivo setting, since it is well established that the paracrine effects of TGFβ (on stromal cells such as immune cells, fibroblasts, endothelial cells, etc., surrounding the tumor epithelial cells) enhance tumor spread. In these cells, km23 would be expected to result in cellular responses similar to those TGFβ induces, and these are essentially all tumor enhancing. Moreover, it is within the contemplation of the present invention that a mutant km23 form, such as the truncated mutant extending from amino acids 1-75, could result in a block to the growth inhibition of cells by km23. Further, an antagonist against such a mutant km23 form could further result in a blockade of the effect of the mutant form, and in such embodiment be able to restore the growth inhibitory effect of km23. Therefore, therapeutic agents can be designed against the truncated form or other mutant forms of km23. Another technique for screening therapeutic agents which may be used is described in PCT Application WO 84/03564. Briefly, in this method, as it is applied to km23, large numbers of different small test compounds are synthesized on a solid support. The test compounds are reacted with km23, or a fragment thereof, and washed. Bound km23 is then detected by methods well known in the art. Alternatively, non-neutralizing antibodies can be used to capture the peptide and immobilize it on a solid support. In another embodiment, one may use competitive therapeutic agent screening assays in which neutralizing antibodies capable of binding km23 specifically compete with a test compound for binding km23 protein. In this manner, the antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with km23 protein. The above methods provide for high through-put screening of compounds having suitable binding affinity to the km23 protein of interest and provide means for modulating its activity, and therefore, that of TGFβ superfamily members. EXAMPLE 1 Preparation of a cDNA expression library from TGFβ-stimulated TEC 4-1 cells The rat IEC line TEC 4-1 (Mulder et al., 1993) was used as a source of RNA for synthesis of the cDNA library to be screened for proteins which interact with the bacterially expressed, phosphorylated TβR intracellular domains. Cells were cultured as previously described and tested for growth inhibition following treatment with TGFβ 3 (10 ng/ml) by a 3 H-thymidine incorporation assay to measure DNA synthesis (Hartsough et al, 1996). To harvest total cellular RNA, IEC 4-1 cells were plated at a density of 6660 cells/cm 2 and were switched to serum-free medium the following day. After 24 h, TGFβ 3 was added to the cell cultures at a concentration of 10 ng/ml and cells were incubated for an additional 3 minutes prior to RNA harvest by a standard protocol (Chirgwin et al., 1979). Messenger RNA was purified via passaging of total cellular RNA over an oligo(dT) cellulose column (Gibco BRL). cDNA synthesis was carried out using the Superscript Choice System for cDNA Synthesis (Gibco BRL). First-strand synthesis was performed using both random oligo- and oligo-dT primers provided by the manufacturer. Double-stranded cDNA ligated to Eco RI adapters was size-selected and fractions were analyzed by agarose gel electrophoresis. Fractions 6 through 8 were pooled and ligated into the Eco RI site of the TriplEx expression vector (Clontech). The ligated DNA was incorporated into phage particles (Gigapack II Gold, Stratagene, La Jolla, CA) and titered by infection of E. coli strain XL 1-Blue. The phage/bacteria mixture was plated onto NZY/agar plates containing IPTG and X-gal following the manufacturer's protocols (Clontech) to determine the titer and percentage of recombinant phage generated. EXAMPLE 2 Screening of the cDNA expression library for proteins which interact with phosphorylated TGFβ receptors Recombinant phage were screened using a modified CORT protocol (Skolnik et al, 1991). The packaged cDNA library was plated at a density of 20,000 plaques/150 mm petri dish. Following incubation of the petri dishes at 42°C for 4 to 5 h to allow for phage growth, plates were overlaid with nitrocellulose filters (Millipore) which had been soaked in 10 mM IPTG for 20 minutes, and the plates were incubated at 37°C for an additional 3 h. Filters were removed and rinsed 3 times in TBST, incubated at room temperature for 1 h in 5% milk/TBST, rinsed an additional 3 times in TBS, and finally incubated overnight at room temp with freshly harvested TβR protein, which had been phosphorylated in an in vitro kinase assay and resuspended in PBS. Typically, the proteins were labeled at a concentration of 15-17 Ci/mmol, which represented between 5 and 10 μg of protein, and were eluted and used for screening 10 filters. Following incubation, filters were washed 3 times at room temperature for 5 min each in TBS. The occurrence of interactions between recombinant 32 P -labeled TβR proteins, and expressed proteins from the cDNA library, were determined by autoradiography. Positive plaques were picked and resuspended in phage buffer SM at 4°C for several hours to elute phage particles. Eluted phage were titered and replated for secondary screening to enrich for positive clones. A third round of screening confirmed the presence of a pure culture of a single clone. To obtain a plasmid containing the positive clone, a single, isolated positive phage plaque was picked from the tertiary screen plate, placed in one ml of SM buffer, and incubated at 4°C for several hours to allow the phage particles to elute. Bacterial strain BM25.8 (Clontech) was grown and infected with the eluted phage particles following the manufacturer's protocol. Briefly, the bacteria were cultured overnight at 31°C in NZY media containing 20 mM maltose and the following day, the culture was supplemented with 1 M M g Cl 2 to a final concentration of 10 mM. Two hundred μl of BM25.8 culture was added to 150 μl of eluted phage and the solution was placed at 31°C for 30 minutes without shaking to allow for infection to take place. Four hundred μl of LB broth was added and the mixture was allowed to grow at 31°C for 1 h with shaking to induce the DNA recombination necessary to generate a plasmid containing the inserted clone. Aliquots of the culture were plated onto LB/agar plates containing carbenicillin. After incubation overnight, a single colony was picked and cultured to obtain plasmid DNA for sequencing and further analysis. EXAMPLE 3 Identification of a km23 protein and isolation of the full-length cDNA The positive clone was sequenced and the generated sequence (approx. 463 bp) was compared by BLAST analysis to sequences published in available databases (Genbank, EST, etc). The DNA insert from the positive clone was removed with Eco RI or Not I digestion and used to screen the phage library to obtain a full-length cDNA copy of the gene. Briefly, phage were plated at a density of 50,000/150 mm plate and incubated overnight. Plaques were lifted onto nitrocellulose filters according to standard protocols and the presence of positive clones was identified using the DNA insert described above which had been labeled with 32 P-dCTP using a random priming kit (Gibco BRL). The resulting clones were picked and rescreened twice to ensure a pure phage clone had been obtained. Plasmid DNA was harvested and sequenced to determine if the entire gene had been isolated. EXAMPLE 4 Cell Culture 293 T cells were obtained from T. Wong (Bristol-Myers Squibb) and were maintained in Dulbecco's Modified Eagle Medium (GibcoBRL, Cat. No. 11995-065) supplemented with 10% fetal bovine serum (FBS). Madin Darby canine kidney (MDCK) cells were obtained from American Type Culture Collection (ATCC, Cat. No. CCL-34) and were maintained in Minimum Essential Medium-α Medium (GibcoBRL, Cat. No. 12561-056) supplemented with 10%) FBS. Cells were routinely subcultured prior to 90-95% confluency using 0.26% trypsin in S-MEM Joklik Modified medium (GibcoBRL, Cat. No. 22300-024) containing 0.1% EDTA. Mink lung epithelial cells (MvlLu/CCL64) were obtained from ATCC and cultured as described previously (Mulder and Morris, 1992; Hartsough and Mulder, 1995). EXAMPLE 5 Transient Transfections 293 T cells were transiently transfected with TGFβ receptors using Lipofectamine Plus (GibcoBRL, Cat. No. 10964-013) according to the manufacturer's instructions. Briefly, cells were plated in 60 mm plates so that the confluency was approx. 50% by 24h later. 3 μg total DNA was added to 0.3 ml PBS and 6ml Plus reagent, followed by addition of 10 ml Lipofectamine and incubation for another 20 min at room temperature. After washing plates with Opti-MEM I (GibcoBRL, Cat. No.31985-070), the DNA/Plus/Lipofectamine solution was applied to the plates for a 4- 6 h incubation at 37°C in 5% CO 2 . MEM 1 20% FBS was then added for 24 h. MDCK (or MvlLu) cells were transiently transfected using Superfect (Qiagen Cat. No. 301305) according to the manufacturer's protocol. Briefly, cells were plated in 60 mm dishes as described for 293 T cells. DNA (10 μg) was added to MEM-α without serum, followed by addition of Superfect. MEM-α 10% FBS (1 ml) was added to the DNA/Superfect solution and then applied to the plates for a 4-6 h incubation at 37°C in 5% CO 2 . Plates were then incubated in MEM-α 10% FBS for approx. 36 h. EXAMPLE 6 1 25 I-TGFβ CROSSLINKING STUDDSS This example describes the crosslinking studies verifying that km23 interacts with the TGFβ receptors. Additional studies performed by the inventor demonstrate that there is a direct interaction between km23 and TGFβ receptors, as determined by immunoprecipitation/blot experiments (not shown). 125 I-TGFβ crosslinking studies were performed essentially as described (Mulder et al, 1993; Zhou et al, 1995a; 1995b; Yue et al, 1999a). Briefly, 293T cells were plated at a density of 4x10 5 cells/cm 2 in T-75 flasks in DMEM medium. The next day, cells were transfected with km23-flag and tagged-TβR's as described for the in vivo phosphorylation assays. Cells were then washed twice with PBS and incubated in serum-free medium for 1 h, followed by incubation in blocking buffer (DMEM, 25mM Hepes, pH 7.4, 2 mg/ml BSA) for 30 min at 37°C. Cells were then incubated with binding buffer (DMEM, 25 mM Hepes, pH 7.4, 5 mg/ml BSA) containing 200 pM 125 I- TGFβi in presence or absence of cold TGFβ (1 nM) for 4 h at 4°C. The labeling medium was removed, and cells were incubated with wash buffer containing 0.3 mM disuccinimidyl suberrate (DSS) for 15 min at 4°C. Cells were washed with termination buffer three times and were lysed with lysis buffer. Cell lysates (200 μl) were immunoprecipitated using either an anti-Flag antibody or mouse IgG. Immunocomplexes were resolved by SDS-PAGE (10%), and gels were dried and exposed to X-ray film at 70°C. Total cell lysates were subjected to immunoblot analysis for confirmation of expression of km23 and receptors. Fig. 4A depicts the results of affinity crosslinking experiments, which indicate that both RI and RII are present in km23-flag immunocomplexes (lane5) from cell lysates of 293 T cells which had been transiently transfected with TGFβ receptors and/or km23 flag, prior to 125 I-TGFβ affinity labeling. As expected, cold TGFβ and IgG controls demonstrated no TGFβ receptors (lanes 6, 7). Immunoblotting controls demonstrating expression of the transfected km23-flag (B), Rl-myc (C) and RII-HA (D) are also shown. Fig. 4B confirms that km23 was present in all lanes corresponding to samples from cells in which it had been expressed. Figs. 4C and 4D demonstrate that Rl-myc or RJJ-HA was present in the expected lanes (2, 5, and 6). Thus, the transfection, expression, and loading aspects of the assays were appropriately performed. The results clearly indicate that the TβR complex can phosphorylate km23. EXAMPLE 7 In Vivo Phosphorylation Assays This example demonstrates that km23 is phosphorylated by the RI RII TGFβ receptor complex. In vivo phosphorylation assays were performed essentially as described previously (Liu et al, 1998; Yue et al, 1999a; b). Briefly, 293T cells were plated in 60 mm dishes at 0.7 x 10 6 cells/cm 2 and were transfected using Lipofectamine Plus (Gibco-BRL) during experimental phase growth. After the 4-h transfection period, Opti-MEM supplemented with 10%> FBS was added for 24 h followed by normal growth medium for an additional 24 h. Cells were then incubated in serum-free, phosphate-free DMEM for 30 min, labeled for 3 h with [ 32 P]-orthophosphate (mCi/ml) at 37°C in 5% CO 2 , washed with cold PBS, and lysed in 120 μl of lysis buffer (1% Triton X-100, 10 Mm Tris [pH 7.6], 50 mM NaCl, 30 mM Na pyrophosphate, 50 Mm NaF, 1 mM PMSF, 1 mM Na orthovanadate, 1 μg/ml aprotinin, 5 mM benzamidine, 1 mM EGTA, pH 8.0, 100 nM okadaic acid) at 4°C for approx 5 min. Insoluble debris was removed by micro-centrifugation at 10,000 rpm for 20 min. The supernatants were then normalized for radioactivity as determined by TCA precipitation. Equal radioactivity of cleared cell lysates were immunoprecipitated for 2 h at 4°C with 10 μg of Anti-Flag M2 monoclonal antibody (Sigma) or Mouse IgG (Sigma), followed by absorption to protein A-agarose (Gibco-BRL). Beads were washed 3 times in lysis buffer without aprotinin and okadaic acid. Bound proteins were eluted by heating in electrophoresis sample buffer containing DTT, and analyzed by SDS-PAGE (6-20%ι gradient). The wet gel was exposed to X-OMAT AR film (Kodak) at -80°C. Proteins on the gel were transferred to an Immobilon-P PVDF membrane (Millipore) and immunoblotted with anti-Flag antibody to detect expression of tagged proteins. As shown in Fig. 5, the TβR complex can phosphorylate km23, whereas no phosphorylation is observed in empty vector or IgG controls (lanes 1, 5). Fig. 5B is the blotting control to demonstrate that km23 was expressed in the relevant samples (lanes 2, 4). As a positive control we were also able to show that Smad 3 was phosphorylated by the TβR complex as expected (data not shown). The results demonstrate that the TβR complex can phosphorylate km23. EXAMPLE 8 Kinetics for TGFβ Induction of km23 Expression in MDCK cells MDCK cells were transiently transfected with km23-flag. 36h after transfection, cells were treated with TGFβ for various time points and then lysed. Total cell lysates were subjected to Western Blot analysis with an anti-flag Ab. Referring to Fig. 6, the presence of the km23 band migrating at approximately 11 kD in lanes 2-7 indicates that TGFβ induces expression of km23 in MDCK cells and that this induction is almost immediate. EXAMPLE 9 km23 induces CRE luciferase reporter activity and TGFβ synergizes with km23 in inducing this effect Luciferase Reporter Assays were performed essentially as described previously (Liu et al, 1998; Yue et al, 1999a; b). Briefly, cells were transiently transfected as described above and the Dual Luciferase Assay System (Promega) was performed according to the manufacuturer's instructions using renilla luciferase as a control for transfection efficiency. Fig. 7A depicts CRE luciferase reporter activity in 293T cells, in the absence and presence of km23, after transfection with either Rl-flag only, RII-HA only, or both TGFβ receptors. As shown, km23 expressed with RII alone was able to stimulate CRE activity by approximately 3-4-fold, whereas expression of RI alone did not. This may be due to the presence of a modest number of endogenous RI receptors in 293T cells. km23 expression with both TGFβ receptors stimulated activity to a greater extent (approximately 7-fold) than did expression of TβR II alone ( 3-4 fold). Controls for expression of the relevant components transfected were as for the other figures. Since 293T cells express a low level of endogenous RI, and since RII controls expression of RI, it cannot be concluded with certainty that RU alone is sufficient to induce CRE activity. However, it is clear that the TβR complex can synergize with km23 to induce CRE-Lux. The data are consistent with km23 being in a signaling pathway for TGFβ activation of CRE activity. Fig. 7B demonstrates that while TGFβ alone had little effect on CRE reporter activity in mink lung epithelial (MvlLu) cells, the combination of km23 and TGFβ synergizes to stimulate CRE activity. MvlLu cells express endogenous TGFβ receptors and are highly TGFβ responsive. These results provide additional evidence that km23 is in a TGFβ signaling pathway, and suggest, further, that other events activated by TGFβ and km23 are involved in this transcriptional effect. EXAMPLE 10 km23 Interacts with Dynein in TGFβ-responsive MDCK cells Referring to Fig. 8, MDCK cells were transiently transfected with either empty vector or km23-flag. 36h after transfection, cells were treated with TGFβ for various time points and then lysed. Cell lysates were subjected to immunoprecipitation using a monoclonal anti-dynein Ab, followed by immunoblot analysis using an anti-flag Ab (A). Cell lysates were then blotted with anti-flag (B) or anti-dynein (C) as a control for expression (B). The presence of the km23 bands in lanes 2-5 (A) indicates that dynein and km23 interact in all samples in which km23 was expressed. Further, the data demonstrate that TGFβ can induce a rapid, time-dependent increase in the interaction between km23 and dynein. This is further evidence that TGFβ can regulate dynein interactions with its associated proteins. This example illustrates that km23 interacts with dynein biochemically in TGFβ-responsive epithelial cells. For these studies, MDCK cells were chosen to be examined, for which DNA synthesis is inhibited by 60% in thymidine incorporation assays after a 24-h treatment with TGFβ. Moreover, MDCK epithelial cells are often utilized in transport studies due to their highly polarized nature. Thus, these cells will transport proteins along polarized MT's and require dynein for such functions. For the studies shown in Fig. 8, we transfected the MDCK cells with km23-flag and performed immunoprecipitation/blot experiments using an anti-flag Ab to immunoprecipitate km23 and its associated proteins, and a monoclonal anti-dynein Ab to detect cytoplasmic dynein in the km23 immunocomplexes. As shown in Fig. 8A, a 74-kD band corresponding to cytoplasmic dynein was only present in lanes 2-5 where km23 had been expressed in the cells. No specific band was observed when km23 was not expressed (lane 1) or in the IgG lane (lane 6), even when different exposures were examined. The results shown in Fig. 8B and C demonstrate that km23 and dynein were present in the relevant lanes (2-6 for km23, 1-6 for dynein), and were equally expressed. The plot in D shows the densitometer scan values for the bands shown in A. Accordingly, km23 interacts with cytoplasmic dynein in TGF(-responsive epithelial cells. Further, this interaction is enhanced by TGFβ in a rapid, time-dependent manner. EXAMPLE 11 km23 interacts with the TGFβ signaling component Smad2 Referring to Fig. 9, 293T cells were transfected with Flag-tagged Smad2 and lysates were incubated with sepharose-bound bacterially expressed GST alone, GST- rkm23, or GST-SBD (Smad-binding domain of SARA, positive control). A: GST- bound proteins were analyzed by SDS-PAGE (10 % ) and were immunoblotted with an anti-flag Ab. Flag-tagged proteins were detected by ECL. Smad 2 interacts with GST- km23 and GST-SBD, but not with GST alone (control). Empty vector (EV) control lanes were also negative. B: Western blot analysis with an anti-Flag Ab to confirm expression of Smad2 in the relevant lanes (2, 4, 6). C: Coomassie staining of gel in A demonstrating the presence of GST and GST fusion proteins in the relevant lanes (2,4,6). The sizes are as expected for the different fusion proteins (approx. 37 kDa for GST-km23, approx. 35 kDa for GST-SBD) or GST alone (approx. 27 kDa). These results demonstrate that km23 interacts with Smad2, a TGFβ superfamily member signaling component known to be important for some biological responses of TGFβ. The interaction suggests that km23 can modulate Smad2 function in some way or vice versa. List of References 1. Ausubel, F.M., et al. (1992), Current Protocols in Molecular Biology, (John Wiley and Sons, New York, N.Y.) 2. Bassing, C.H., Yingling, J.M., Howe, D. I, Wang, T, He, W.W., Gustafson, ML., Shah, P., Donahoe, P.K., and Wang, X.-F. (1994) A transforming growth factor β type I receptor that signals to activate gene expression. Science 263:87-89. 3. Bilder, D., Li, M., and Perrimon, N. (2000) Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289: 113-116. 4. Bowman, A.B., Patel-King, R.S., Benashski, S.E., McCaffery, J.M., Goldstein, L.S.B., and King, S.M. (1999) Drosophila roadlbock and Chlamydomonas LC7: A conserved family of dynein-associated proteins involved in axonal transport, flagellar motility, and mitosis. J. Cell Biol. 146: 165-179. 5. Buard, A., Zipfel, P.A., Frey, R.S., and Mulder, K.M. (1996) Maintenance of growth factor signaling through Ras in human colon carcinoma cells containing K- ras mutations. Int. J. Cancer 67:539-546. 6. 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(1991) Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases. Cell 65:83-90. 36. Smolik-Utlaut, S.M., (1990) Dosage requirements of Ultrahithorax and bithoraxoid in the determination of segment identity of Drosophila melanogaster. Genetics 124:357-366. 37. Sporn, M.B., Roberts, A.B., Wakefield, L.M., and de Crombrugghe, B. (1987) Some recent advances in the chemistry and biology of transforming growth factor- beta. J. Cell. Biol. 105:1039-1045. 38. Sporn, M.B. and Vilcek, J.T., eds. Cytokine and Growth Factor Reviews - TGFβ Special Issue 11:1-168, 2000. 39. Stern, D.L., A role of Ultrahithorax in morphological differences between Drosophila species, Nature 396: 463-466, 1998. 40. Tsukazaki, T., Chiang, T.A., Davison, A.F., Attisano, L. and Wrana, J.L. (1998) SARA, a FYVE domain protein that recruits Smad2 to the TGFβ receptor. Cell 95:779-791. 41. Ventura, F., Liu, F., Doody, J., and Massague, J. 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Claims: WHAT IS CLAIMED IS: 1. An isolated or recombinant km23 polypeptide, fragment thereof, or mutant form thereof in a pharmaceutical composition suitable for humans which mediates or modulates the intracellular signal transduction activity of at least one transforming growth factor β (TGFβ) superfamily member. 2. The polypeptide of claim 1, wherein said polypeptide comprises an amino acid sequence represented in the general formula of SEQ JD NO: 1. 3. The polypeptide of claim 1 wherein said pharmaceutical composition further comprises a biocompatible pharmaceutical carrier. 4. The polypeptide of claim 1 wherein said pharmaceutical composition comprises clinical grade sterile water. 5. The polypeptide of claim 1 wherein said polypeptide or fragment interacts with a TGFβ receptor. 6. The polypeptide of claim 1 wherein said polypeptide or fragment binds to at least one signaling component for the TGFβ superfamily members. 7. The polypeptide of claim 6 wherein said signaling component comprises Smad2. 8. The polypeptide of claim 1 wherein said polypeptide or fragment is of a mammal. 9. The polypeptide of claim 1 wherein said polypeptide or fragment interacts with dynein. 10. An isolated or recombinant polypeptide, fragment thereof, or mutant form thereof in a pharmaceutical composition suitable for humans comprising an amino acid sequence which is of the same superfamily as a km23 polypeptide according to claim 1. 11. An isolated or recombinant km23 polypeptide fragment or mutant form thereof wherein said fragment mediates or modulates the intracellular signal transduction activity of at least one TGFβ superfamily member. 12. The fragment of claim 11 wherein said fragment interacts with TGFβ receptors. 13. The fragment of claim 11 wherein said fragment binds to at least one signaling component for the TGFβ superfamily members. 14. The fragment of claim 11 wherein said fragment is of a vertebrate organism. 15. The fragment of claim 11 wherein said fragment is of a mammal. 16. The fragment of claim 15 comprising the amino acid sequence corresponding to amino acids 1-25 in SEQ ID NO: 1 or SEQ ID NO: 2. 17. The fragment of claim 15 comprising the amino acid sequence corresponding to amino acids 2-96 in SEQ ID NO: 1 or SEQ ID NO: 2. 18. The fragment of claim 15 comprising the amino acid sequence corresponding to amino acids 16-96 in SEQ ID NO: 1 or SEQ ID NO: 2. 19. The fragment of claim 15 comprising the amino acid sequence corresponding to amino acids 1-31 in SEQ ID NO: 1 or SEQ ID NO: 2. 20. The fragment of claim 15 comprising the amino acid sequence corresponding to amino acids 19-96 in SEQ ID NO: 1 or SEQ ID NO: 2. 21. The fragment of claim 15 comprising the amino acid sequence corresponding to amino acids 32-96 in SEQ ID NO: 1 or SEQ ID NO: 2. 22. The fragment of claim 15 comprising the amino acid sequence corresponding to amino acids 1-47 in SEQ ID NO: 1 or SEQ ID NO: 2. 23. The fragment of claim 15 comprising the amino acid sequence corresponding to amino acids 1-60 in SEQ ID NO: 1 or SEQ ID NO: 2. 24. The fragment of claim 15 comprising the amino acid sequence corresponding to amino acids 1-75 in SEQ ID NO: 1 or SEQ ID NO: 2. 25. The fragment of claim 15 comprising the amino acid sequence corresponding to amino acids 1-89 in SEQ ID NO: 1 or SEQ ID NO: 2. 26. The fragment of claim 11 comprising functional consensus phosphorylation sites. 27. The fragment of claim 11 wherein said fragment antagonizes intracellular signal transduction pathways mediated by TGFβ superfamily members. 28. The fragment of claim 11 wherein said fragment stimulates intracellular signal transduction pathways mediated by TGFβ superfamily members. 29. The fragment of claim 11 wherein said fragment interacts with dynein. 30. The fragment of claim 29 wherein the interaction with dynein is modulated by TGFβ superfamily members. 31. An isolated or recombinant polypeptide fragment or mutant form thereof comprising an amino acid sequence which is of the same superfamily as a km23 polypeptide fragment according to claim 11. 32. An isolated or recombinant km23 polypeptide in a pharmaceutical composition which functions in a growth factor or cytokine signaling pathway. 33. An isolated or recombinant mutant km23 polypeptide which modulates a growth factor or cytokine signaling pathway. 34. An isolated or recombinant km23 polypeptide fragment or a mutant form thereof which functions in a growth factor or cytokine signaling pathway. 35. A mutant km23 polypeptide or a fragment thereof which mediates or modulates the intracellular signal transduction activity of at least one TGFβ superfamily member. 36. The mutant km23 polypeptide of claim 35 wherein said mutant polypeptide is selected from the group consisting of: (a) a mutant km23 polypeptide having a Met at the amino acid corresponding to amino acid number 22 of SEQ ID NO: 1 or SEQ ID NO: 2; (b) a mutant km23 polypeptide having a Lys at the amino acid corresponding to amino acid number 25 of SEQ ID NO: 1 or SEQ ID NO: 2; (c) a mutant km23 polypeptide having a Asp at the amino acid corresponding to amino acid number 26 of SEQ ID NO: 1 or SEQ ID NO: 2; (d) a mutant km23 polypeptide having a Val at the amino acid corresponding to amino acid number 35 of SEQ ID NO: 1 or SEQ ID NO: 2; (e) a mutant km23 polypeptide having a Leu at the amino acid corresponding to amino acid number 37 of SEQ ED NO: 1 or SEQ ID NO: 2; (f) a mutant km23 polypeptide having a Glu at the amino acid conesponding to amino acid number 41 of SEQ ID NO: 1 or SEQ ED NO: 2; (g) a mutant km23 polypeptide having a Cys at the amino acid corresponding to amino acid number 42 of SEQ ED NO: 1 or SEQ ED NO: 2; (h) a mutant km23 polypeptide having a Asn at the amino acid corresponding to amino acid number 44 of SEQ ED NO: 1 or SEQ ID NO: 2; (i) a mutant km23 polypeptide having a Pro at the amino acid corresponding to amino acid number 45 of SEQ ID NO: 1 or SEQ ID NO: 2; (j) a mutant km23 polypeptide having a Leu at the amino acid corresponding to amino acid number 46 of SEQ ED NO: 1 or SEQ ED i NO: 2; (k) a mutant km23 polypeptide having a Met or Ala at the amino acid conesponding to amino acid number 57 of SEQ ID NO: 1 or SEQ ID NO: 2; (1) a mutant km23 polypeptide having a Val, His, Asp, or Gly at the amino acid corresponding to amino acid number 58 of SEQ ED NO: 1 or SEQ ID NO: 2; (m) a mutant km23 polypeptide having a Glu or Asn at the amino acid conesponding to amino acid number 59 of SEQ DD NO: 1 or SEQ ED NO: 2; (n) a mutant km23 polypeptide having a Ser at the amino acid corresponding to amino acid number 60 of SEQ ED NO: 1 or SEQ ED NO: 2; (o) a mutant km23 polypeptide having a Cys at the amino acid corresponding to amino acid number 72 of SEQ ED NO: 1 or SEQ ED NO: 2; (p) a mutant km23 polypeptide comprising a truncated mutant km23 protein corresponding to amino acid number 1 to amino acid 75 of SEQ ED NO: 1 or SEQ ID NO: 2. 37. A cloned km23 nucleic acid form of SEQ DD NO : 5. 38. A cloned km23 nucleic acid form comprising a nucleotide sequence encoding a km23 polypeptide wherein said nucleic acid form comprises a pharmaceutical composition suitable for humans. 39. A cloned km23 nucleic acid form comprising a nucleotide sequence encoding a km23 polypeptide fragment or mutant form thereof. 40. The nucleic acid of claim 37 further comprising a 5' or 3' regulatory sequence. 41. The nucleic acid of claim 38 further comprising a 5' or 3' regulatory sequence. 42. The nucleic acid of claim 39 further comprising a 5' or 3' regulatory sequence. 43. The nucleic acid of claim 38 wherein said regulatory sequence is operably linked to nucleotide sequence encoding a km23 polypeptide. 44. The nucleic acid of claim 39 wherein said regulatory sequence is operably linked to nucleotide sequence encoding a km23 polypeptide fragment. 45. The nucleic acid of claim 38 wherein said km23 polypeptide is of a mammal. 46. The nucleic acid of claim 39 wherein said km23 polypeptide fragment is of a mammal. 47. The nucleic acid of claim 38 wherein said polypeptide comprises amino acid 1 to the C-terminus in SEQ ED NO: 1 or SEQ DD NO:2. 48. The nucleic acid of claim 39 wherein said polypeptide fragment comprises the amino acid sequence corresponding to amino acids 1-25 or 1-31 in SEQ ED NO: 1 or SEQ DD NO: 2. 49. The nucleic acid of claim 39 wherein said polypeptide fragment comprises the amino acid sequence corresponding to amino acids 2-96 in SEQ ED NO: 1 or SEQ DD NO: 2. 50. The nucleic acid of claim 39 wherein said polypeptide fragment comprises the amino acid sequence corresponding to amino acids 16-96 in SEQ ED NO: 1 or SEQ ED NO: 2. 51. The nucleic acid of claim 39 wherein said polypeptide fragment comprises the amino acid sequence corresponding to amino acids 19-96 in SEQ DD NO: 1 or SEQ DD NO: 2. 52. The nucleic acid of claim 39 wherein said polypeptide fragment comprises the amino acid sequence corresponding to amino acids 32-96 in SEQ DD NO: 1 or SEQ DD NO: 2. 53. The nucleic acid of claim 39 wherein said polypeptide fragment comprises the amino acid sequence corresponding to amino acids 1-47 in SEQ DD NO: 1 or SEQ DD NO: 2. 54. The nucleic acid of claim 39 wherein said polypeptide fragment comprises the amino acid sequence corresponding to amino acids 1-60 in SEQ ED NO: 1 or SEQ DD NO: 2. 55. The nucleic acid of claim 39 wherein said polypeptide fragment comprises the amino acid sequence corresponding to amino acids 1-75 in SEQ ED NO: 1 or SEQ DD NO: 2. 56. The nucleic acid of claim 39 wherein said polypeptide fragment comprises the amino acid sequence corresponding to amino acids 1-89 in SEQ ED NO: 1 or SEQ DD NO: 2. 57. A cloned mutant km23 nucleic acid form, wherein said mutant form mediates or modulates the intracellular signal transduction activity of at least one TGFβ superfamily member. 58. The cloned mutant km23 nucleic acid form of claim 57 wherein said mutant is characterized by a mutation of at least one nucleotide base relative to a wild-type km23 nucleic acid form which mutation results in a mutant km23 polypeptide selected from the group consisting of: (a) a mutant km23 polypeptide having a Met at the amino acid corresponding to amino acid number 22 of SEQ DD NO: 1 or SEQ ED NO: 2; (b) a mutant km23 polypeptide having a Lys at the amino acid corcesponding to amino acid number 25 of SEQ DD NO: 1 or SEQ DD NO: 2; (c) a mutant km23 polypeptide having a Asp at the amino acid corresponding to amino acid number 26 of SEQ DD NO: 1 or SEQ ED NO: 2; (d) a mutant km23 polypeptide having a Val at the amino acid corresponding to amino acid number 35 of SEQ DD NO: 1 or SEQ DD NO: 2; (e) a mutant km23 polypeptide having a Leu at the amino acid corresponding to amino acid number 37 of SEQ DD NO: 1 or SEQ DD NO: 2; (f) a mutant km23 polypeptide having a Glu at the amino acid corresponding to amino acid number 41 of SEQ DD NO: 1 or SEQ ED NO: 2; (g) a mutant km23 polypeptide having a Cys at the amino acid corresponding to amino acid number 42 of SEQ ED NO: 1 or SEQ ED NO: 2; (h) a mutant km23 polypeptide having a Asn at the amino acid corresponding to amino acid number 44 of SEQ DD NO: 1 or SEQ DD NO: 2; (i) a mutant km23 polypeptide having a Pro at the amino acid corresponding to amino acid number 45 of SEQ DD NO: 1 or SEQ DD NO: 2; (j) a mutant km23 polypeptide having a Leu at the amino acid conesponding to amino acid number 46 of SEQ DD NO: 1 or SEQ DD NO: 2; (k) a mutant km23 polypeptide having a Met or Ala at the amino acid conesponding to amino acid number 57 of SEQ DD NO: 1 or SEQ DD NO: 2; (1) a mutant km23 polypeptide having a Val, His, Asp, or Gly at the amino acid corresponding to amino acid number 58 of SEQ ED NO: 1 or SEQ DD NO: 2; (m) a mutant km23 polypeptide having a Glu or Asn at the amino acid corcesponding to amino acid number 59 of SEQ ED NO: 1 or SEQ ED NO: 2; (n) a mutant km23 polypeptide having a Ser at the amino acid corresponding to amino acid number 60 of SEQ ED NO: 1 or SEQ ED NO: 2; (o) a mutant km23 polypeptide having a Cys at the amino acid conesponding to amino acid number 72 of SEQ DD NO: 1 or SEQ DD NO: 2; (p) a mutant km23 polypeptide comprising a truncated mutant km23 protein corresponding to amino acid number 1 to amino acid 75 of SEQ DD NO: l or SEQ D NO: 2. 59. A fusion protein comprising a km23 polypeptide or a mutant form thereof and a second polypeptide having an amino acid sequence unrelated to the amino acid sequence of said km23 polypeptide. 60. The fusion protein of claim 59 wherein said second polypeptide functions as a detectable label for detecting the presence of said fusion protein or as a matrix-binding domain for immobilizing said fusion protein. 61. A cloned nucleic acid molecule encoding a fusion protein according to claim 59. 62. An expression vector capable of expressing in a host cell a km23 polypeptide, fragment thereof or mutant form thereof. 63. The expression vector of claim 62 wherein the km23 polypeptide, fragment or mutant form thereof mediates or modulates the intracellular signal transduction activity of at least one TGFβ superfamily member. 64. The expression vector of claim 62 wherein the km23 polypeptide, fragment, or mutant form thereof is capable of modulating at least one of the group consisting of regulation of gene expression, cell growth, cell differentiation, cell survival, apoptosis, senescence, cell migration, angiogenesis, fibrosis, wound healing, extracellular matrix induction, adhesion, autoproduction, embryogenesis and combinations thereof. 65. The expression vector of claim 62 wherein the km23 polypeptide, fragment or mutant form thereof is capable of modulating at least one of the group consisting of actin cytoskeleton dynamics, microtubule dynamics, intracellular transport, cell polarity, dynein-mediated microtubule transport and combinations thereof. 66. A host cell transfected with the expression vector of claim 62. 67. The host cell of claim 66 wherein the polypeptide is modulated by a TGFβ superfamily member. 68. A substantially pure oligonucleotide or primer, said oligonucleotide or primer comprising a region of nucleotide sequence capable of hybridizing under stringent conditions to at least about 12 consecutive nucleotides of sense or antisense sequence of a nucleic acid according to claim 37. 69. A substantially pure oligonucleotide or primer, said oligonucleotide or primer comprising a region of nucleotide sequence capable of hybridizing under stringent conditions to at least about 12 consecutive nucleotides of sense or antisense sequence of a nucleic acid according to claim 38. 70. A substantially pure oligonucleotide or primer, said oligonucleotide or primer comprising a region of nucleotide sequence capable of hybridizing under stringent conditions to at least about 12 consecutive nucleotides of sense or antisense sequence of a nucleic acid according to claim 39. 71. A substantially pure oligonucleotide or primer, said oligonucleotide or primer comprising a region of nucleotide sequence capable of hybridizing under stringent conditions to at least about 12 consecutive nucleotides of sense or antisense sequence of a nucleic acid according to claim 57. 72. The oligonucleotide of claim 68 wherein said oligonucleotide further comprises a detectable label attached thereto. 73. The oligonucleotide of claim 69 wherein said oligonucleotide further comprises a detectable label attached thereto. 74. The oligonucleotide of claim 70 wherein said oligonucleotide further comprises a detectable label attached thereto. 75. The oligonucleotide of claim 71 wherein said oligonucleotide further comprises a detectable label attached thereto. 76. A method of mediating or modulating the signal transduction activity of at least one TGFβ superfamily member, the method comprising introducing into the cell a km23 polypeptide, fragment thereof or mutant form thereof. 77. The method of claim 76 wherein said km23 polypeptide, fragment or mutant form thereof is introduced into the cell by expressing in the cell a nucleic acid molecule that encodes the polypeptide or fragment. 78. The method of claim 76 wherein said km23 polypeptide, fragment or mutant form thereof is introduced into the cell by contacting the cell with the polypeptide or fragment. 79. The method of claim 76 wherein said km23 polypeptide comprises approximately amino acids 1 to the C-terminus in SEQ DD NO:l or SEQ DD NO:2. 80. The method of claim 76 wherein said fragment comprises the amino acid sequence corresponding to amino acids 1-25 in SEQ ED NO: 1 or SEQ DD NO: 2. 81. The method of claim 76 wherein said fragment comprises the amino acid sequence corresponding to amino acids 2-96 in SEQ DD NO: 1 or SEQ DD NO: 2. 82. The method of claim 76 wherein said fragment comprises the amino acid sequence corresponding to amino acids 16-96 in SEQ DD NO: 1 or SEQ DD NO: 2. 83. The method of claim 76 wherein said fragment comprises the amino acid sequence corresponding to amino acids 1-31 in SEQ DD NO: 1 or SEQ DD NO: 2. 84. The method of claim 76 wherein said fragment comprises the amino acid sequence corresponding to amino acids 19-96 in SEQ ED NO: 1 or SEQ ED NO: 2. 85. The method of claim 76 wherein said fragment comprises the amino acid sequence corresponding to amino acids 32-96 in SEQ DD NO: 1 or SEQ DD NO: 2. 86. The method of claim 76 wherein said fragment comprises the amino acid sequence corresponding to amino acids 1-47 in SEQ ED NO: 1 or SEQ DD NO: 2. 87. The method of claim 76 wherein said fragment comprises the amino acid sequence corresponding to amino acids 1-60 in SEQ DD NO: 1 or SEQ DD NO: 2. 88. The method of claim 76 wherein said mutant form comprises the amino acid sequence corresponding to amino acids 1-75 in SEQ ED NO: 1 or SEQ DD NO: 2. 89. The method of claim 76 wherein said fragment comprises the amino acid sequence corresponding to amino acids 1-89 in SEQ ED NO: 1 or SEQ DD NO: 2 90. The method of claim 76 wherein the cell is a malignant cell. 91. The method of claim 76 wherein the cell is a carcinoma. 92. The method of claim 76 wherein the cell is a osteocarcinoma, sarcoma, osteosarcoma, glioma, melanoma, myxoma, adenoma, rhabdomyoma-derived cell, or pre-malignant versions thereof. 93. The method of claim 76 wherein the cell is a lung, breast, colon, prostate, kidney, ovary, liver, testes, skin, heart, pancreas, thyroid, adrenal, pituitary, brain, muscle, uterine or bone cell. 94. The method of claim 76 wherein the cell is a metastasized cell. 95. The method of claim 76 wherein the cell is a post-embryonic cell. 96. The method of claim 76 wherein the cell is an embryonic cell. 97. A method of inhibiting cell growth, the method comprising introducing into the cell a km23 polypeptide, or a fragment thereof. 98. The method of claim 97 wherein the cell is a malignant cell. 99. The method of claim 97 wherein the cell is a carcinoma. 100. The method of claim 97 wherein said km23 polypeptide, or a fragment thereof is introduced into the cell by expressing in the cell a nucleic acid molecule that encodes the polypeptide or fragment thereof. 101. The method of claim 97 wherein said km23 polypeptide or a fragment thereof is introduced into the cell by contacting the cell with the km23 polypeptide or fragment thereof. 102. A method of modulating at least one of the group consisting of regulation of gene expression, cell growth, cell differentiation, cell survival, apoptosis, senescence, cell migration, angiogenesis, fibrosis, wound healing, extracellular matrix induction, adhesion, autoproduction, embryogenesis and combinations thereof, the method comprising introducing into the cell a km23 polypeptide, fragment thereof or mutant form thereof. 103. A method of modulating at least one of the group consisting of actin cytoskeleton dynamics, microtubule dynamics, intracellular transport, cell polarity, dynein-mediated microtubule transport and combinations thereof, the method comprising introducing into the cell a km23 polypeptide, fragment thereof or mutant form thereof. 104. A method of modulating the signal transduction activity of at least one TGFβ superfamily member, the method comprising introducing into the cell an agonist of a km23 nucleic acid form, or an agonist of amino acids encoded by said nucleic acid form. 105. A method of modulating the signal transduction activity of at least one TGF β superfamily member, the method comprising introducing into the cell an antagonist of a km23 nucleic acid form, or an antagonist of amino acids encoded by said nucleic acid form. 106. The method of claim 105 wherein said km23 nucleic acid form includes mutant km23 forms. 107. The method of claim 105 wherein the antagonist of the km23 nucleic acid form is an antisense construct. 108. The method of claim 105 wherein the antagonist of the km23 nucleic acid form is a peptide antagonist. 109. The method of claim 108 wherein the peptide antagonist changes cellular localization of the km23 protein. 110. The method of claim 105 wherein the km23 nucleic acid form is mammalian. 111. The method of claim 105 wherein the antagonist of amino acids encoded by the km23 nucleic acid form is a dominant negative version of the km 23 protein or a hormone-inducible or drug-inducible version thereof. 112. The method of claim 105 wherein the antagonist of amino acids encoded by the km23 nucleic acid form is a monoclonal antibody. 113. A method of modulating at least one of the group consisting of regulation of gene expression, cell growth, cell differentiation, cell survival, apoptosis, senescence, cell migration, angiogenesis, fibrosis, wound healing, extracellular matrix induction, adhesion, autoproduction, embryogenesis and combinations thereof, the method comprising introducing into the cell an agonist of a km23 nucleic acid form, or an agonist of amino acids encoded by said nucleic acid form. 114. A method of modulating at least one of the group consisting of actin cytoskeleton dynamics, microtubule dynamics, intracellular transport, and cell polarity, dynein-mediated microtubule transport and combinations thereof, the method comprising introducing into the cell an agonist of a km23 nucleic acid form or an agonist of amino acids encoded by said nucleic acid form. 115. A method of modulating at least of the group consisting of regulation of gene expression cell growth, cell differentiation, cell survival, apoptosis, senescence, cell migration, angiogenesis, fibrosis, wound healing, extracellular matrix induction, adhesion, autoproduction, embryogenesis and combinations thereof, the method comprising introducing into the cell an antagonist of a km23 nucleic acid form or an antagonist of amino acids encoded by said nucleic acid form. 116. The method of claim 115 wherein said km23 nucleic acid form includes mutant km23 forms. 117. A method of modulating at least one of the group consisting of actin cytoskeleton dynamics, microtubule dynamics, intracellular transport, and cell polarity, dynein-mediated microtubule transport and combinations thereof, the method comprising introducing into the cell an antagonist of a km23 nucleic acid form or an antagonist of amino acids encoded by said nucleic acid form 118. The method of claim 117 wherein said km23 nucleic acid form includes mutant km23 forms. 119. A monoclonal antibody that binds specifically to an antigenic determinant in a km23 polypeptide or mutant forms thereof. 120. The monoclonal antibody of claim 119 wherein the km23 polypeptide functions in a growth factor or cytokine signaling pathway. 121. The monoclonal antibody of claim 119 wherein the km23 polypeptide is a human polypeptide. 122. A method for identifying therapeutic agents that inhibit, potentiate, or mimic the ability of a km23 polypeptide, mutant form thereof, or a nucleic acid encoding the polypeptide or mutant form thereof, to modulate the signal transduction activity of a growth factor or cytokine, the method comprising: (a) treating a cell with an effective amount of at least one candidate so as to alter at least one of the group consisting of regulation of gene expression, cell growth, cell differentiation, cell survival, apoptosis, senescence, cell migration, angiogenesis, fibrosis, wound healing, extracellular matrix induction, adhesion, autoproduction, embryogenesis and combinations thereof; and (b) measuring the effect of the candidate on the cell. 123. The method of claim 122 wherein said candidates are therapeutic agents that modulate or mediate at least one of said group by an amount at least 10% relative to the cell in the absence of said candidates. 124. A method for identifying therapeutic agents that inhibit, potentiate, or mimic the ability of a km23 polypeptide, mutant form thereof, or a nucleic acid encoding the polypeptide, or mutant form thereof, to modulate the signal transduction activity of a growth factor or cytokine, the method comprising: (a) treating a cell with an effective amount of at least one candidate so as to alter at least one of the group consisting of actin cytoskeleton dynamics, microtubule dynamics, intracellular transport, cell polarity, dynein- mediated microtubule transport and combinations thereof; and (b) measuring the effect of the candidate on the cell. 125. The method of claim 124 wherein said candidates are therapeutic agents that modulate or mediate at least one of said group by an amount at least 10% relative to the cell in the absence of said candidates. 126. A method of determining if a patient is at risk for a disorder or has a disorder, the method comprising detecting, in a patient specimen, the presence or absence of a lesion characterized by an alteration in sequence, expression, post-translational modification, or some combination thereof of km23 nucleic acid or polypeptide forms. 127. The method of claim 126 wherein the presence or absence of a lesion is characterized by: (a) a mutation of a gene encoding a km23 polypeptide or a homolog thereof; (b) a mis-expression of said gene; (c) an altered signal transduction activity of said polypeptide and combinations thereof. 128. A transgenic animal having cells which harbor a transgene encoding a km23 polypeptide or a fragment thereof. 129. A transgenic animal having cells in which a gene for a km23 polypeptide or a fragment thereof is disrupted. 130. A method for producing a km23 polypeptide, fragment thereof or mutant form thereof, the method comprising: (a) culturing the host cell of claim 66 under conditions suitable for the expression of the polypeptide or fragment; and (b) recovering the polypeptide or fragment from the host cell culture. 131. A method for detection of km23 nucleic acid forms in a biological sample, the method comprising: (a) hybridizing km23 nucleic acid forms to nucleic acid material of a biological sample, thereby forming a hybridization complex; and (b) detecting said hybridization complex, wherein the presence of said complex correlates with the presence of km23 nucleic acid forms in said biological sample. 132. The method of claim 131 wherein said km23 nucleic acid forms include mutant km23 nucleic acid forms. 133. A method for detection of km23 nucleic acid forms comprising the steps of: (a) amplifying a km23 nucleic acid form of a biological sample; and (b) detecting sequence alternations in said biological sample. 134. The method of claim 133 wherein said km23 nucleic acid forms include mutant km23 nucleic acid forms. 135. A method for detection of a km23 polypeptide form comprising performing an immunoassay thereon. 136. The method of claim 135 wherein said km23 polypeptide is a fragment, a mutant, an activated form or an inactivated form of km23. 137. A method of restoring the growth inhibitory activity of at least one TGFβ superfamily member, the method comprising introducing into the cell an antagonist of a mutant km23 polypeptide form. 138. The method of claim 137 wherein the mutant form blocks the growth inhibitory activity of the TGFβ superfamily member. 139. The method of claim 137 wherein said antagonist is a therapeutic agent.

Inventors: MULDER KATHLEEN M, MULDER, KATHLEEN, M.
Applicants: MULDER KATHLEEN M, MULDER, KATHLEEN, M.
Application year: 2001
Main classification: C07K14
IPC codes: A61K38, A61K48, C07K14