PTP-D SUBFAMILY OF PROTEIN TYROSINE PHOSPHATASES

Abstract: A novel subfamily (PTP-D) of protein tyrosine phosphatases is identified. Included in this family are PTP-D proteins or glycoproteins having one, two, or three identified amino acid changes in previously defined consensus sequences in the catalytic phosphatase domains of known protein tyrosine phosphatases. The PTP-D proteins or glycoproteins may be produced by recombinant means. Antibodies to PTP-D proteins or glycoproteins and nucleic acid constructs coding therefor, and methods for screening molecules which can bind to PTP-D proteins or glycoproteins and inhibit or stimulate their enzymatic activity, are provided.

Description: PTD-D SUBFAMILY OF PROTEIN TYROSINE PHOSPHATASES BACKGROUND OF THE INVENTION Field of the Invention The invention pertains to the field of biochemistry and cell and molecular biology. The invention relates to PTP-D proteins or glycoproteins that are members of a novel subfamily (PTP-D) of protein tyrosine phosphatases (PTPases), nucleic acid constructs coding for PTP-D proteins or glycoproteins, recombinant expression vectors carrying the nucleic acid constructs, cells containing the recombinant expression vectors, methods for production and identification of PTP-D proteins and glycoproteins and DNA constructs coding ϊherefor, antibodies specific for PTP-D proteins and glycoproteins, and methods for screening compounds capable of binding to and inhibiting or stimulating protein tyrosine phosphatase enzymatic activity of PTP-D proteins or glycoproteins. Description of the Background Technology Phosphorylation of proteins is a fundamental mechanism for regulating diverse ce.Vular processes. While the majority of protein phosphorylation occurs at serine and threonine residues, phosphorylation at tyrosine residues is attracting a great deal of interest since the discovery that many oncogene products and growth factor receptors possess intrinsic protein tyrosine kinase activity. The importance of protein tyrosine phosphorylation in growth factor signal transduction, ce\\ cycle progression and neoplastic transformation is now well established (Hunter et al., Ann. Rev. Biochem. 54:987-930 (1985), Ullrich et al., Cell 61 .203-212 (1990), Nurse, Nature 344:503-508 (1990), Cantley et al., Cell 64:281-302 (1991)). Biochemical studies have shown that phosphorylation on tyrosine residues of a variety of cellular proteins is a dynamic process involving competing phosphorylation and dephosphorylation reactions. The regulation of protein tyrosine phosphorylation is mediated by the reciprocal actions of protein tyrosine kinases (PTKases) and protein tyrosine phosphatases (PTPases). The tyrosine phosphorylation reactions are catalyzed by PTKases. Tyrosine phosphorylated proteins can be specifically dephosphorylated through the action of PTPases. The level of protein tyrosine phosphorylation of intracellular substances is determined by the balance of PTKase and PTPase activities. (Hunter, T., Cell 55: 1013-1016 (1989)). PTKases The protein tyrosine kinases (PTKases) are a large family of proteins that includes many growth factor receptors and potential oncogenes. (Hanks et al., Science 241:42-52 (1988)). Many PTKases have been linked to initial signals required for induction of the cell cycle (Weaver et al., Mol. and Cell. Biolx 11 (9)'Λ415-4422 (1991)). PTKases comprise a discrete family of enzymes having common ancestry with, but major differences from, serine/threonine-specific protein kinases (Hanks et al., supra). The mechanisms leading to changes in activity of PTKases are best understood in the case of receptor-rvpe PTKases having a transmembrane topology (Ullrich et al. (1990) supra). The binding of specific ligands to the extracellular domain of members of receptor-type PTKases is thought to induce their oligomerization leading to an increase in tyrosine kinase activity and activation of the signal transduction pathways (Ullrich et al., (1990) supra). Deregulation of kinase activity through mutation or overexpression is a well- established mechanism for cell transformation (Hunter et al., (1985) supra; Ullrich et al., (1990) supra). PTPases The protein phosphatases are composed of at least two separate and distinct families (Hunter, T.(1989) supra) the protein serine/threonine phosphatases and the protein tyrosine phosphatases (PTPases). The protein tyrosine phosphatases (PTPases) are a family of proteins that have been classified into two subgroups. The first subgroup is made up of the low molecular weight, intracellular enzymes that contain a single conserved catalytic phosphatase domain. All known intracellular type PTPases contain a single conserved catalytic phosphatase domain. Examples of the first group of PTPases include (1) placental PTPase IB (Charbonneau et al., Proc. Natl. Acad. Sci. USA 86:5252-5256 (1989); Chernoff et al., Proc. Natl. Acad. Sci. USA £7:2735-2789 (1989)), (2) T-cell PTPase (Cool et al. Proc. Natl. Acad. Sci. USA 86:5257-5261 (1989)), (3) rat brain PTPase (Guan et al., Proc. Natl. Acad. Sci. USA 57:1501-1502 (1990)), (4) neuronal phosphatase (STEP) (Lombroso et al.,Proc. Natl. Acad. Sci. USA 55:7242-7246 (1991)), and (5) cytoplasmic phosphatases that contain a region of homology to cytoskeletal proteins (Gnet al., Proc. Natl. Acad. Sci. USA 55:5867-57871 (1991); Yang et al, Proc. Natl. Acad. Sci. USA 55:5949-5953 (1991)). The second subgroup is made up of the high molecular weight, receptor-linked PTPases, termed R-PTPases. R-PTPases consist of a) an intracellular catalytic region, b) a single transmembrane segment, and c) a putative ligarid-binding extracellular domain (Gebbink et al., supra). The structures and sizes of the c) putative ligand-binding extracellular "receptor" domains of R-PTPases are quite divergent. In contrast, the a) intracellular catalytic regions of R-PTPases are highly homologous. All R- PTPases have two tandemly duplicated catalytic phosphatase homology domains, with the prominent exception of an R-PTPase termed HPTP/3, which has only one catalytic phosphatase domain. (Tsai et al., Journal of Biol. Chem. 266(16): 10534-10543 (1991)). One example of R-PTPases are the leukocyte common antigens (LCA) (Ralph, S.J., EMBO J. 6: 1251-1257 (1987)). LCA is a family of high molecular weight glycoproteins expressed on the surface of all leukocytes and their hemopoietic progenitors (Thomas, Ann. Rev. Immunol. 7:339-369 (1989)). A remarkable degree of similarity is detected with the sequence of LCA from several species (Charbonneau et al. , Proc. Natl. Acad. Sci. USA 55:7182-7186 (1988)). LCA is referred to in the literature by different names, including T200 (Trowbridge et al., Eur. J. Immunol. 6:557-562 (1962)), B220 for the B cell form (Coffman et al., Nature 259:681-683 (1981)), the mouse allotypic marker Ly-5 (Komuro et al., Immuno 'genetics i. '452-456 (1975)), and more recently CD45 (Cobbold et al., Leucocyte Typing III, ed. A.J. McMichael et al., pp. 788-803 (1987)). Several studies suggest that CD45 plays a critical role in T cell activation. These studies are reviewed in Weiss A., Ann. Rev. Genet. 25:487-510 (1991). In one study, T-cell clones that were mutagenized by NSG and selected for their failure to express CD45 had impaired responses to T-cell receptor stimuli (Weaver et al., (1991) supra). These T-cell clones were functionally defective in their responses to signals transmitted through the T cell antigen receptor, including cytolysis of appropriate targets, proliferation, and tymphokine production (Weaver et al. , (1991) supra). Other studies indicate that the PTPase activity of CD45 plays a role in the activation of pp56 lc , a lymphocyte-specific PTKase (Mustelin et al., Proc. Natl. Acad. Sci. USA 56:6302-6306 (1989); Ostergaard et al., Proc. Natl. Acad. Sci. USA 56:8959-8963 (1989)). These authors hypothesized that the phosphatase activity of CD45 activates pp56 Ick by dephosphorylation of a C- terminal tyrosine residue, which may, in turn, be related to T-cell activation. Another example of R-PTPases is the leukocyte common antigen related molecule (LAR) (Streuli et al., J. Exp. Med. 765: 1523-1530 (1988)). LAR was initially identified as a homologue of LCA (Streuli et al, supra). Although the a) intracellular catalytic region of the LAR molecule contains two catalytic phosphatase homology domains (domain I and domain II), mutational analyses suggest that only domain I has catalytic phosphatase activity, whereas domain II is enzymatically inactive (Streuli et al., EMBO J. 9(5J:2399-2407 (1990)). Chemically induced LAR mutants having tyrosine at amino acid position 1379 changed to a phenylalanine are temperature-sensitive (Tsai et al., J. Biol. Chem. 266(16): 10534-10543 (1991)). A new mouse R-PTP, designated mRPTP , has been cloned which has a) an extracellular domain that shares some structural motifs with LAR. (Gebbink et al., (1991) supra). In addition, these authors have cloned the human homologue of RPTPμ and localized the gene on human chromosome 18. Two Drosophila PTPases, termed DLAR and DPTP, have been predicted based on the sequences of cDNA clones (Streuli et al., Proc. Natl. Acad. Sci. USA 56:8698-8702 (1989)). cDNAs coding for another Drosophila R-PTPase, termed DPTP 99A, have been cloned and characterized (Hariharan et al., Proc. Natl. Acad. Sci. USA 55: 11266-11270 (199Ϊ)). Other examples of R-PTPases include R-PTPase-α, β, y, and f (Krueger et al., EMBO J. 9:3241-3252 (1990), Sap et al. Proc. Natl. Acad. Sci. USA 57::6112-6116 (1990), Kaplan et al., Proc. Natl. Acad. Sci. USA 57:7000-7004 (1990), Jirik et al., FEBS Lett. 275:239-242 (1990), Mathews et al., Proc. Natl. Acad. Sci. USA 57:4444-4448 (1990), Ohagi et al., Nucl. Acids Res. 75:7159 (1990)). Published application WO92/01050 discloses human R-PTPase-α, β and 7, and reports on the nature of the structural ho ologies found among the conserved domains of these three R-PTPases and other members of this protein family. The murine R-PTPase-α has 794 amino acids, whereas the human R-PTPase-α has 802 amino acids. R-PTPase-α has an intracellular domain homologous to the catalytic domains of other tyrosine phosphatases. The 142 amino acid extracellular domain (including signal peptide of R-PTPase-α) has a high serine and threonine content (32%) and 8 potential N-glycosylation sites. cDNA clones have been produced that code for the R-PTPase-α, and R-PTPase-α has been expressed from eukaryotic hosts. Northern analysis has been used to identify the natural expression of R-PTPase-α in various cells and tissues. A polyclonal antibody to R-PTPase-α has been produced by immunization with a synthetic peptide of R-PTPase-α, which identifies a 130 kDa protein in cells transfected with a cDNA clone encoding a portion of R-PTPase-α. Another example of R-PTPases is HePTP. (Jirik et al, FASEB J. 4:82082 (1990) Abstract 2253). Jirik et al. screened a cDNA library derived from a hepatoblastoma cell line, HepG2, with a probe encoding the two PTPase domains of LCA, and discovered a cDNA clone encoding a new R- PTPase, named HePTP. The HePTP gene appeared to be expressed in a variety of human and murine cell lines and tissues. Since the initial purification, sequencing, and cloning of a PTPase, additional potential PTPases have been identified at a rapid pace. The number of different PTPases that have been identified is increasing steadily, leading to speculations that this family may be as large as the PTKase family (Hunter (1989) supra). Conserved amino acid sequences in the catalytic domains of known PTPases have been identified and defined (Krueger et al., EMBO J. 9:3241- 3252 (1990) and Yi et al., Mol. Cell. Biol. 72:836-846 (1992), which are incorporated herein by reference.) These amino acid sequences are designated "consensus sequences" herein. Yi et al. aligned the catalytic phosphatase domain sequences of the following PTPases: LCA, PTP1B, TCPTP, LAR, DLAR, and HPTPα, HPTP3, and HPTP7. This alignment includes the following "consensus sequences" (Yi et al., supra, Figure 2(A), lines 1 and 2): 1. D Y I N A S/N [SEQ. ID NO: 1] Krueger et al., aligned the catalytic phosphatase domain sequences of PTP1B, TCPTP, LAR, LCA, HPTPα, β, 8, e and f, and DLAR and DPTP. This alignment includes the following "consensus sequences: (Krueger et al., supra, Figure 7, lines 1 and 2): 1. D/N Y I N A S/N [SEQ. ID NO. 4] It is becoming clear that dephosphorylation of tyrosine residues can by itself function as an important regulatory mechanism. Dephosphorylation of a C-terminal tyrosine residue has been shown to activate tyrosine kinase activity in the case of the src family of tyrosine kinases (Hunter, T. Cell 49: 1- 4 (1987)). Tyrosine dephosphorylation has been suggested to be an obligatory step in the mitotic activation of the maturation-promoting factor (MPF) kinase (Morla et a , Celt 58:193-203 (1989)). These observations point out the need in the an for understanding the mechanisms that regulate tyrosine phosphatase activity. It is clear that further analysis of structure-function relationships among PTPases are needed to gain important understanding of the mechanisms of signal transduction, cell cycle progression and cell growth, and neoplastic transformation. DEFINITIONS Table I gives the single-letter abbreviations for amino acids that are in common use among protein chemists and are used herein. Amino Acid Name Symbol The inventors describe herein the identification of a novel subfamily (PTP-D) of protein tyrosine phosphatases. The novel subfamily, hereinafter "PTP-D subfamily, " differs significantly in structure from previously reported PTPases. The present invention thus provides a PTP-D protein or glycoprotein which is a PTPase from the PTP-D subfamily. Preferably, a PTP-D protein or glycoprotein comprises a PTPase from the PTP-D subfamily of PTPases having catalytic phosphatase domains in which amino acid sequences are selected from: 1. G Y I N A S/N [SEQ ID NO.5] 2. S X X Y W P [SEQ. ID NO.6] 3. IAMVXXXXE [SEQ. ID NO.7] The amino acid sequences selected from 1. G Y I N A S/N [SEQ. ID NO.5] 2. S X X Y W P [SEQ. ID NO.6] 3. IAMVXXXXE [SEQ. ID NO.7] have the following amino acid differences in comparison with the previously defined amino acid consensus sequences in the catalytic phosphatase domains of PTPases (differences are underlined): 1. PTP-D: GYINAS/N " [SEQ. ID NO.5] Consensus D Y I N A S/N [SEQ. ID NO.1] N Y I N A S/N [SEQ. ID NO.8] 2. PTP-D 1/D2 SXXYWP [SEQ. ID NO.6] Consensus C X X Y W P [SEQ. ID NO.2] 3. PTP-D 1/D2 IAMVXXXXE [SEQ. ID NO.7] Consensus (I/V/L) V (M/I/L) (V/L/I/M) X X X X E [SEQ. ID NO.9] When a PTP-D,protein or glycoprotein of the invention is one which occurs in nature, it is substantially free of other proteins or glycoproteins with which it is natively associated. A substantially pure PTP-D protein or glycoprotein of the invention may be produced by biochemical purification of the glycoprotein. Alternatively, a PTP-D protein or glycoprotein of the invention may be prepared by chemical means or by recombinant means in the prokaryotic or eukaryotic hosts, and is provided substantially free of other proteins with which it is natively associated and/or has modified amino acids. The invention is further directed to a fragment of a PTP-D protein or glycoprotein, to a PTP-D protein or glycoprotein having additional amino acids, and to a PTP-D protein or glycoprotein having substituted amino acids, and to a PTP-D protein or glycoprotein having any combination of deleted, additional, or substituted amino acids, such that the PTP-D protein or glycoprotein possesses the desired biological activity. The invention is further directed to a nucleic acid construct comprising a nucleotide sequence encoding a PTP-D protein or glycoprotein according to the invention in the form of cDN A or ge.iomic DNA. The invention is fuπher directed to a nucleic acid construct in the form of an expression vehicle, as well as prokaryotic and eukaryotic host cells containing the expression vehicle. Also included in the present invention is a process for preparing a PTP- D protein or glycoprotein of this invention, comprising: (a) culturing a host capable of expressing a PTP-D protein or glycoprotein under culturing conditions, (b) expressing the PTP-D protein or glycoprotein; and (c) recovering the PTP-D protein or glycoprotein from the culture. The invention is also directed to an antibody, polyclonal antibody, monoclonal antibody, or chimeric antibody, specific for a PTP-D protein or glycoprotein or for an epitope of a PTP-D protein or glycoprotein. The invention is fuπher directed to a method for detecting the presence, or measuring the quantity, of a PTP-D protein or glycoprotein in cell or in a subject comprising: (a) contacting said cell or an extract thereof with an antibody specific for an epitope of a PTP-D protein or glycoprotein; and (b) detecting the binding of the antibody to the cell or extract thereof, or measuring the quantity of antibody bound, thereby detecting the presence or measuring the quantity of the PTP-D protein or glycoprotein. The invention is also directed to a method for detecting the presence of a nucleic acid construct encoding a normal or mutant PTP-D protein or glycoprotein in a cell or a subject comprising: (a) contacting a cell or an extract thereof from the subject with an oligonucleotide probe encoding at least a portion of a normal or mutant PTP-D protein or glycoprotein under hybridizing conditions; and (b) measuring the hybridization of the probe to nucleic acid of the cell, thereby detecting the presence of the nucleic acid construct. The nucleic acid of the cell can be selectively amplified, using the polymerase chain reaction, prior to assay. The present invention is also directed to a method for identifying and isolating in a chemical or biological preparation a compound capable of binding to a PTP-D protein or glycoprotein, said method comprising: (a) attaching a PTP-D protein or glycoprotein or the compound- binding portion thereof to a solid phase matrix; (b) contacting the chemical or biological preparation with the solid phase matrix allowing the compound to bind, and washing away any unbound material; (c) detecting the presence of the compound bound to the solid phase; and, for purposes of isolation, (d) eluting the bound compound, thereby isolating the compound. Finally, the< invention includes a method for identifying a molecule capable of stimulating or inhibiting the enzymatic activity of a PTP-D protein or glycoprotein, comprising: (a) contacting the compound with a PTP-D protein or glycoprotein in pure form, in a membrane preparation, or in a whole live or fixed cell; (b) incubating the mixture in step (a) for a sufficient interval; (c) measuring the enzymatic activity of the PTP-D protein or glycoprotein; (d) comparing the enzymatic activity to that of the PTP-D protein or glycoprotein incubated without the compound, thereby determining whether the molecule stimulates or inhibits the activity. A fragment of a PTP-D protein or glycoprotein may be used in this method for identifying a molecule capable of stimulating or inhibiting the activity. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 presents the paπial cDNA sequence and tnj deduced amino acid sequence of PTP-D 1, which is a PCR fragment. Figure 2 presents the partial cDNA sequence and the deduced amino acid sequence of PTP-D2, which is a PCR fragment. Figure 3A shows a comparison of the deduced amino acid sequences of PTP-D 1 and PTP-D2 with the amino acid sequence of PTPase IB. The CLUSTAL program is used (Higgins, C, Fuch, R. and Bleasby, D., Multiple Sequence Alignment; CABIOS (1991) (in press)). Figure 3B shows a comparison of the nucleotides between PTP-D 1 and PTP-D2. Figure 3C shows a comparison of the amino acids between PTP-D 1 and PTP-D2. Figure 4 shows the partial cDNA sequence and the deduced amino acid sequence of PTP-D 1. This partial cDNA sequence includes the cDNA sequence of the PCR fragment shown in Figure 1. DETAILED DESCRIPTION OF THE INVENTION The inventors have identified a new subfamily ('PTP-D subfamily') of protein tyrosine phosphatases (PTPases) which structurally differs significantly from previously reported PTPases. Members of this PTP-D subfamily are characterized by having one, two, or three of the following amino acid differences in comparison with the previously defined amino acid consensus sequences in the catalytic phosphatase domains of PTPases (differences are underlined): 1. PTP-D: GYINAS/N [SEQ. ID NO.5] . Consensus D Y I N A S/N [SEQ. ID NO.1] N Y I N A S/N [SEQ. ID NO.8] 2. PTP-D 1/D2 SXXYWP [SEQ. ID NO.6] Consensus C X X Y W P [SEQ. ID NO.2] 3. PTP-D1/D2 IAMVXXXXE [SEQ. ID NO.7] Consensus (I/V/L) V (M/I/L) (V/L/IM) X X X X E [SEQ. ID NO.9] The term "subfamily" is used to indicate a group of PTPases which are structurally related at specific amino acid residues as specified above. By previously defined amino acid consensus sequences is meant the conserved amino acid sequences in the catalytic phosphatase domains of known PTPases described in Krueger et al, EMBO J.9:3241-3252 (1990) and Yi et al, Mol. Cell. Biol.72:836-846 (1992), which are incorporated herein by reference. Accordingly, the present invention relates to a PTP-D protein or glycoprotein comprising a PTPase from the PTP-D subfamily of PTPases having a catalytic phosphatase domain having one, two, or three amino acid sequences selected from: 1. GYINAS/N [SEQ. ID NO.5] 2. SXXYWP [SEQ. ID NO.6] 3. IAMVXXXXE [SEQ. ID NO.7] At present it is not known whether the PTP-D proteins and glycoproteins of the new PTP-D subfamily of PTPases are receptor-linked PTPases or intracellular PTPases. In one aspect, the invention is directed to a naturally occurring mammalian PTP-D protein or glycoprotein. In another aspect, the invention is directed to a recombinant mammalian PTP-D protein or glycoprotein. In another aspect, the invention is directed to a chemically synthesized mammalian PTP-D protein or glycoprotein. The preferred PTP-D protein or glycoproteins of the present invention are of human origin. The invention provides a naturally occurring PTP-D protein or glycoprotein substantially free of other proteins or glycoproteins with which it is natively associated. "Substantially free of other proteins or glycoproteins" indicates that the PTP-D protein or glycoprotein has been purified away from at least 90 per cent (on a weight basis), and from even at least 99 per cent if desired, of other proteins and glycoproteins with which it is natively associated, and is therefore substantially free of them. That can be achieved by subjecting the cells, tissue or fluids containing the PTP-D protein or glycoprotein to standard protein purification techniques such as immunoadsorbem columns bearing monoclonal antibodies reactive against the protein. Other forms of affinity purification can utilize solid-phase substrates which can bind the catalytic phosphatase domain, or a ligand that will bind to the receptor domain that may be present in a PTP-D protein or glycoprotein. Alternatively, the purification can be achieved by a combination of standard methods, such as ammonium sulfate precipitation, molecular sieve chromatography, and ion exchange chromatography. It will be understood that a mammalian PTP-D protein or glycoprotein of the present invention can be biochemically purified from a variety of cell or tissue sources. For preparation of a naturally occurring PTP-D protein or glycoprotein, tissues such as skeletal muscle, especially of human origin, are preferred. Cell lines, such as rhabdemyosarcoma cell lines (RD) may be used. Alternatively, because the gene for a PTP-D protein or glycoprotein can be isolated or synthesized, a PTP-D protein can be synthesized substantially free of other proteins or glycoproteins of mammalian origin in a prokaryotic organism or in a non-mammalian eukaryotic organism, if desired. As intended by the present invention, a recombinant PTP-D protein or glycoprotein produced in mammalian cells, such as transfected COS, NIH- 3T3, or CHO cells, for example, is either a naturally occurring protein sequence or is a modified protein sequence wherein there are amino acid deletions and/or insertions and/or substitutions. Where a naturally occurring PTP-D protein or glycoprotein is produced by recombinant means, it is provided substantially free of the other proteins and glycoproteins with which it is natively associated. Alternatively, methods are well known for the synthesis of polypeptides of desired sequence on solid phase supports and their subsequent separation from the support. In a further aspect, the invention provides a fragment of a PTP-D protein or glycoprotein. The term "fragment" is used to indicate a polypeptide which is derived from a PTP-D protein or glycoprotein having a naturally occurring protein sequence by appropriately modifying the DNA sequence encoding the PTP-D protein or glycoprotein, resulting in deletion of one or more amino acids at one or more sites of the C-terminal, N-terminal, and within the native sequence. Fragments of a PTP-D protein or glycoprotein are useful for screening for compounds that are antagonists or agonists (as defined below). It is understood that such fragments of a PTP-D protein or glycoprotein may retain characterizing portion(s) of the native PTP-D or glycoprotein. In particular, such fragments of PTP-D proteins or glycoproteins should retain one or more biological activities or functions which are characteristic for the intact PTP-D proteins or glycoproteins. Examples, which are not intended to be in any way limiting to the scope of the invention claimed, of PTP-D fragments are: a) the catalytic domain; b) regions of the PTP-D proteins or glycoproteins which interact with other molecules in the intact cell; c) regulatory parts of PTP-D. In a further aspect, the invention provides a PTP-D protein or glycoprotein having additional amino acids that is derived from a naturally occurring PTP-D protein or glycoprotein by appropriately modifying the DNA sequence encoding the PTP-D protein or glycoprotein, resulting in addition of one or more amino acids at one or more sites of the C-terminal, N-terminal, and within the native sequence. It is understood that such PTP-D protein or glycoprotein having additional amino acids may retain characterizing portion(s) of the native PTP-D protein or glycoprotein. In particular, such PTP-D proteins or glycoproteins with additional amino acids should retain one or more biological activities or functions which are characteristic for the intact PTP-D proteins or glycoproteins. Examples of such characteristics, of which at least one should be retained: a) the catalytic activity; b) the substrate specificity; c) interaction with other molecules in the intact cell; d) regulatory functions of PTP-D. These examples are not intended to be in any way limiting to the scope of the invention claimed. In a further aspect, the invention provides a PTP-D protein or glycoprotein having substituted amino acids that is derived from a naturally occurring PTP-D protein or glycoprotein by appropriately modifying or mutating the DNA sequence encoding the PTP-D protein or glycoprotein, resulting in substitution of one or more amino acids at one or more sites of the C-terminal, N-terminal, and within the native amino acid sequence. It is understood that such PTP-D protein or glycoprotein having substituted amino acids may retain characterizing portion(s) of • the PTP-D protein or glycoprotein.. In particular, such PTP-D proteins or glycoproteins having substituted amino acids should retain one or more biological activities or functions which are characteristic for the intact PTP-D proteins or glycoproteins. Examples of such characteristics, of which at least one should be retained: a) the catalytic activity; b) the substrate specificity; c) interaction with other molecules in the intact cell; d) regulatory functions of PTP-D. These examples are not intended to be in any way limiting to the scope of the invention claimed. Any combination of deletion, insertion, and substitution may also be made to arrive at the final construct of a PTP-D protein or glycoprotein, provided that the final construct possesses the desired activity or function present in the intact PTP-D proteins or glycoproteins. Examples of such activities and functions are: a) the catalytic activity; b) substrate specificity; c) interaction with. other molecules in vitro and in vivo; d) regulatory functions. Only one of such activities or functions needs to be retained after any combination of deletion, insertion, and substitution. These examples are not intended to be in any way limiting to the scope of the invention claimed. Obviously, the modifications or mutations that will be made in the DNA encoding the PTP-D protein or glycoprotein must not alter the reading frame and preferably will not create complementary regions that could produce secondary mRNA structure (see European Patent Publication No. EP 75,444). At the genetic level, these PTP-D proteins or glycoproteins having deletions from, and/or insertions to, and/or substitutions of amino acids,- ordinarily are prepared by site-directed mutagenesis (as exemplified by Adelman et al, DNA 2: 183 (1983)) of nucleotides in the DNA encoding the peptide molecule, thereby producing DNA encoding the PTP-D protein or glycoprotein, and thereafter expressing the DNA in recombinant cell culture (see below). The PTP-D protein or glycoproteins having amino acid deletions and/or insertions and/or additions typically exhibit the same qualitative biological activity as a native PTP-D protein or glycoprotein. Alternatively, a PTP-D protein or glycoprotein having amino acid deletions and/or insenions and/or substitutions may be conveniently prepared by direct chemical synthesis, using methods well-known in the art. In a further aspect, the invention provides so-called chimeric molecules which are made up of other PTPases in which one or more specific amino acid sequences are replaced with homologous sequence(s) from a PTP-D protein or glycoprotein. Chimeric molecules include, for example, a PTP-D protein or glycoprotein having a ligand-binding extracellular domain from another PTPase that is grafted onto a portion of the PTP-D protein or glycoprotein. Other chimeric molecules: a) other PTPases in which the catalytic phosphatase domain has been replaced with the phosphatase domain from a PTP-D protein. In this case, the preferred number of amino acids is between 220 and 260. b) A PTP-D protein or glycoprotein in which part or parts of the catalytic domain has been replaced with homologous part(s) from other PTPases. c) chimeric molecules consisting of one member of the PTP-D subfamily in which a part or parts have been replaced with homologous parts. from one (or more) other member(s) from the PTP-D subfamily. "Homologous sequences" are defined as sequences in two or more PTPases which are similarly positioned in the primary sequence and which may exhibit sequence homology. It should be emphasized that "homologous sequences" should not be limited to cases with high degree of homology. Chimeric molecules are important tools for elucidating structure-function relationships and for identifying specific compounds (drugs). Therefore, the most useful chimeras are often, but not always, molecules in which a certain portion of one molecule has been replaced with the similarly positioned, but divergent, sequence from another, otherwise homologous, molecule. Thus, the exchanged portions will quite often represent the parts of the molecules where they differ the most. A PTP-D protein or glycoprotein may contain additional chemical moieties not normally a part of the PTP-D protein or glycoprotein. Covalent modifications are included within the scope of this invention. Such modifications may be introduced into die PTP-D protein or glycoprotein by reacting targeted amino acid residues of the PTP-D protein or glycoprotein with an organic derivatizing agent that is capable of reacting with selected side chains or terminal residues. Cysteinyl residues most commonly are reacted with alpha-haloacetates (and corresponding amines), such as chloroacetic acid or chloroacetamide, to give carboxylmethyl or carboxyamidomethyl derivatives. Cysteinyl residues also are derivatized by reaction with bromotrifluoroacetone, alpha-bromo-beta- (5-imidozoyl) propionic acid, chloroacetyl phosphate, N-alkylmaleimides, 3- nitro-2-pyridyl disulfide, methyl 2-pyridyl disulfide, p-chloromercuribenzoate, 2-chloromercuri-4-nitrophenol, or chloro-7-nitrobenzo-2-oxa-l,3-diazole. Histidyl residues are derivatized by reaction with diethylprocarbonate at pH 5.5-7.0 because this agent is relatively specific for the histidyl side chain. Para-bromophenacyl bromide also is useful; the reaction is preferably performed in 0.1 M sodium cacodylate at pH 6.0. Lysinyl and amino terminal residues are reacted with succinic or other carboxylic acid anhydrides. Derivadzation with these agents has the effect or reversing the charge of the lysinyl residues. Other suitable reagents for derivatizing alpha-amino-containing residues include imidoesters such as methyl picolinimidate; pyήdoxiύ phosphate; pyridoxal; chloroborohydride; trinϊtrobenzenesulfonic acid; O-methylisourea; .2,4 pentanedione; and transaminase-catalyzed reaction with glyoxylate. Arginyl residues are modified by reaction with one or several conventional reagents, among them phenylglyoxal, 2,3-butanedione, 1,2- cyclohexanedione, and ninhydrin. Derivatizadon of arginine residues requires that the reaction be - tτiormed in alkaline conditions because of the high pK. of the guanidine functional group. Furthermore, these reagents may react with the groups of lysine as well as the arginine epsilon-amino group. The specific modification of tyrosyl residues per se has been studied extensively, with particular interest in introducing spectral labels into tyrosyl residues by reaction with aromatic dizonium compounds or tetranitromethane. Most commonly, N-acetylimidizol and tetranitromethane are used to form O- acetyl tyrosyle specie and 3-nitro derivatives, respectively. Carboxyl side groups (aspaπyl or glutamyl) are selectively modified by reaction carbodiimide (R'-N-C-N-R') such as l-cyclohexyl-3-(2-morpholinyl- (4-ethyl) carbodiimide or l-ethyl-3-(4-azonia-4,4-dimethylpentyl) carbodiimide. Fuπhermore, aspartyl and glutamyl residue are converted to asparaginyl and glutaminyl residues by reaction with ammonium ions. Glutaminyl and asparaginyl residues are frequently deamidated to the corresponding glutamyl and aspartyl residues. Alternatively, these residues are deamidated under mildly acidic conditions. Either form of these residues falls within the scope of this invention. Derivatization with bifunctional agents is useful for cross-linking the peptide to a water-insoluble support matrix or to other macromolecular carriers. Commonly used cross-linking agents include, e.g., 1,1- bis(diazoacetyl)-2-phenylethane,glutaraIdehyde,N-hydroxysuccinimideesters, for example, esters with 4-azidosalicycIic acid, homobifunctional imidoesters, including dissuccinimidyl esters such as 3,3'-dithiobis(succinimidyl- propionate), and bifunctional maleimides such as bis-N-maleimido-l,8-octane. Derivatizing agents such as methyl-3-[p-azidophenyl)dithio]propioimidate yield photoactivatable intermediates that are capable of forming crosslinks in the presence of light. Alternatively, reactive water-insoluble matrices such as cyanogen bromide-activated carbo hydrates and the reactive substrates described in U.S. Patent Nos. 3,969,287; 3,691,016; 4,195,128; 4,247,642; 4,229,537; and 4,330,440 are employed for protein immobilization. Other modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the alpha-amino groups of lysine, arginine, and histidine side chains {Creighton, T.E., Proteins: Structure and Molecule Properties, W.H. Freeman & Co., San Francisco, pp. 79-86 (1983)), acetylation of the N- terminal amine, and, in some instances, amidation of the C-terminal carboxyl groups. Such derivatized moieties may improve the solubility, absorption, biological half life, and the like. The moieties may alternatively eliminate or attenuate any undesirable side effect of the protein and the like. Moieties capable of mediating such effects are disclosed, for example, in Remington 's Pharmaceutical Sciences, 16th ed., Mack Publishing Co., Easton, PA (1980). In a further aspect, the present invention relates to a PTP-D protein or glycoprotein as defined above having domains which show 70% or more identity to the amino acid sequences of PTP-D 1 or PTP-D2, as provided in Figures 1 and 2, respectively. PTP-D1 and PTP-D2 are PTP-D proteins that are members of the PTP-D subfamily that are expressed in human skeletal muscle. In another aspect, the present invention relates to a PTP-D protein or glycoprotein comprising PTP-D 1 or PTP-D2. Members of the PTP-D subfamily, PTP-D1 and PTP-D2, have been shown to be expressed in human skeletal muscle. Thus, the present invention relates to but is not in any way limited to such members of the PTP-D 1 and PTP-D2 PTP-D subfamily expressed in this tissue- In another aspect, the present invention relates to a nucleic acid construct which comprises a nucleotide sequence encoding a PTP-D protein or glycoprotein, or encoding a PTP-D protein or glycoprotein having amino acid deletions and/or insertions and/or substitutions. The invention is further directed to the nucleic acid sequence in the form of an expression vector such as a recombinant expression vector, as well as prokaryotic and eukaryotic host cells containing the expression vector. In additional aspects of the present invention, methods for expressing a nucleic acid construct encoding a PTP-D protein or glycoprotein are provided. PTP-D protein or glycoproteins may be produced by culturing cells in a suitable nutrient medium under conditions which are conducive to die expression of such PTP-D protein or glycoproteins. One of ordinary skill in the art will know how to identify and clone additional PTP-D protein or glycoproteins, " of human or other mammalian species, which have sequence homology to me PTP-D protein or glycoproteins described herein, using die nucleic acid construct and oligonucleotides of the present invention without undue experimentation. Furthermore, manipulation of the nucleic acid of the present invention allow the grafting of a particular ligand-binding extracellular domain from a particular PTPase onto portions of a PTP-D protein or glycoprotein resulting in chimeric PTP-D proteins or glycoproteins. Non- limiting examples of such chimeric molecules- include the PTP-D protein or glycoprotein having a ligand-binding extracellular domain that is an epidermal growth factor receptor, a fibroblast growth factor receptor, and the like. Genetically engineered chimeric receptors are known in the art (see, for example, Riedel et al, Nature 524:628-670 (1986)). Nucleic acid constructs encoding a PTP-D protein or glycoprotein, and encoding a PTP-D protein or glycoprotein having amino acid deletions and/or insertions and/or substitutions, and encoding chimeric PTP-D proteins or glycoproteins such as those described above, can be used in gene therapy. An abnormal or dysfunctional PTP-D protein or glycoprotein which results in disease, may be replaced by infusion of cells of the desired lineage (such as hemopoietic cells, for example) transfected with a normal PTP-D protein or glycoprotein. Alternatively, or additionally, cells carrying a chimeric PTP-D protein or glycoprotein having a receptor to a ligand of choice (e.g. EGF) can be used for such gene therapy. The nucleic acid constructs that are recombinant DNA molecules of the present invention can be produced through any of a variety of means, such as, for example, DNA or RNA synthesis, or more preferably, by recombinant DNA techniques. Techniques for synthesizing such molecules are disclosed by, for example, Wu et al (Prog. Nucl. Acid. Res. Molec. Biol. 27: 101-141 (1978)). Procedures for constructing recombinant molecules in accordance with the above-described method are disclosed by Sambrook et al , Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor Press, Cold Spring Harbor, NY (1989). The 3' terminus of the recombinant DNA molecule of this invention is preferably treated to render it unsuitable for polymerization. Such treatment may be accomplished by blocking the terminus by chemical means, or by modifying the terminal bases such that they sterically interfere with polymerase action. In a preferred embodiment, such treatment is accomplished by immobilizing the 3' terminus, such as by coupling it to a solid suppoπ (such as, for example, glass, plastic, latex, etc.). The suppoπ may be of any form, (for example, a sheet, rod, sphere, ovoid, etc. Procedures for such immobilization are well known to these of ordinary skill. In the most preferred embodiment, the 3' end of the recombinant DNA molecule is covalently bound to the solid suppoπ. A spacer region may be used to extend the probe outward from the solid suppoπ as long as (1) it will not sterically hinder any function or characteristic of the recombinant molecule, and (2) the sequence of the spacer region does not paπicipate in die hybridization or polymerization reactions of me assay. It is typically desirable to immobilize several, and preferably, a large number of such recombinant DNA molecules to the support. Oligonucleotides representing a portion of a PTP-D protein or glycoprotein are useful for screening for the presence of genes encoding such PTP-D proteins and glycoproteins and for the cloning of PTP-D genes. Techniques for synthesizing such oligonucleotides are disclosed by, for example, Wu et al. (supra). Protein molecules are fragmented as with cyanogen bromide, or with proteases such as papain, chymotrypsin, trypsin, etc. (Oike et al , J. Biol. Chem. 257:9751-9758 (1982); Liu et al., Int. J. Pept. ProteinRes. 27:209-215 (1983)). Because the genetic code is degenerate, more than one codon may be used to encode a particular amino acid (Watson, J.D., In: Molecular Biology of the Gene, 4th Ed., Benjamin/Cummings Publishing Co., Inc., Menlo Park, CA (1987)). Using the genetic code, one or more different oligonucleotides can be identified, each of which would be capable of encoding the amino acid. The probability that a particular oligonucleotide will, in fact, constitute the actual XXX-encoding sequence can be estimated by considering abnormal-, base pairing relationships and the frequency with which a particular codon is actually used (to encode a particular amino acid) in eukaryotic cells. Such "codon usage rules" are disclosed by Lathe et al , J. Molec. Biol. 755: 1-12 (1985). Using the "codon usage rules" of Lathe, a single oligonucleotide, or a set of oligonucleotides, that contains a theoretical "most probable" nucleotide sequence capable of encoding the PTP-D sequences is identified. Although occasionally an amino acid sequences may be encoded by only a single oligonucleotide, frequently the amino acid sequence may be encoded by any of a set of similar oligonucleotides. Importantly, whereas all of the members of this -set contain oligonucleotides which are capable of encoding the peptide fragment and, thus, potentially contain the same oligonucleotide sequence as the gene which encodes the peptide fragment, only one member of the set contains the nucleotide sequence that is identical to the nucleotide sequence of the gene. Because this member is present within the set, and is capable of hybridizing to DNA even in the presence of the other members of the set, it is possible to employ the unfractionated set of oligonucleotides in the same manner in which one would employ a single oligonucleotide to clone the gene that encodes the peptide. The oligonucleotide, or set of oligonucleotides, containing the theoretical "most probable" sequence capable of encoding the PTP-D fragment is used to identify the sequence of a complementary oligonucleotide or set of oligonucleotides which is capable of hybridizing to the "most probable" sequence, or set of sequences. An oligonucleotide containing such a complementary sequence can be employed as a probe to identify and isolate a PTP-D gene (Sambroo et al., supra). A suitable oligonucleotide, or set of oligonucleotides, which is capable of encoding a fragment of a PTP-D gene (or which is complementary to such an oligonucleotide, or set of oligonucleotides) is identified (using the above- described procedure), synthesized, and hybridized by means well known in the aπ, against a DNA or, more preferably, a cDNA preparation derived from cells which are capable of expressing a PTP-D gene. Single stranded oligonucleotide molecules complementary to the "most probable" PTP-D peptide encoding sequences can be synthesized using procedures which are well known to those of ordinary skill in the aπ (Belagaje et al , J. Biol Chem. 254:5765-5 '80 (1979); Maniatis et al, In: Molecular Mechanisms in the Control of Gene Expression, Nieriich et al. Ed., Acad. Press, NY (1976); Wu et al , Prog. Nucl Acid Res. Molec. Biol. 27:101-141 (1978); Khorana, R.G., Science 203:614-625 (1979)). Additionally, DNA synthesis may be achieved through the use of automated synthesizers. Techniques of nucleic acid hybridization are disclosed by Sambrook et al, (supra), and by Haymes et al, (In: Nucleic Acid Hybridization, A Practical Approach, IRL Press, Washington, DC (1985)), which references are herein incorporated by reference. Techniques such as, or similar to, those described above have successfully enabled the cloning of genes for human aldehyde dehydrogenases (Hsu et al, Proc. Natl Acad. Sci. USA 52:3771-3775 (1985)), fibronectin (Suzuki et al , EMBO J. 4:2519-2524 (1985)), the human estrogen receptor gene (Walter et al , Proc. Natl Acad. Sci. USA 52:7889-7893 (1985)), tissue- type plasminogen activator (Pennica et al , Nature 301:214-221 (1983)) and human term placental alkaline phosphatase complementary DNA (K-am et al , Proc. Natl Acad. Sci. USA S2:(715-8719 (1985)). In an alternative way of cloning a PTP-D gene, a lihrary of expression vectors is prepared by cloning DNA or, more preferably, cDNA (from a cell capable of expressing PTP-D) into an expression vector. The library is then screened for members capable of expressing a protein which binds to anti- PTP-D antibody, and which has a nucleotide sequence that is capable of encoding potypepiides that have the same amino acid sequence as PTP-D, or fragments thereof. In this embodiment, DNA, or more preferably cDNA, is extracted and purified from a cell which is capable of expressing PTP-D protein. The purified cDNA is fragmented (by shearing, endonuclease digestion, etc.) to produce a pool of DNA or cDNA fragments. DNA or cDNA fragments from this pool are then cloned into an expression vector in order to produce a genomic library of expression vectors whose members each contain a unique cloned DNA or DNA fragment. An "expression vector" is a vector which (due to the presence of appropriate transcriptional and/or translational control sequences) is capable of expressing a DNA (or cDNA) molecule which- has been cloned into the vector and of thereby producing a polypeptide or protein. Expression of the cloned sequences occurs when the expression vector is introduced into an appropriate host cell. If a prokaryotic expression vector is employed, then the appropriate host cell would be any prokaryotic cell capable of expressing the cloned sequences. Similarly, if a eukaryotic expression vector is employed, then the appropriate host cell would be any eukaryotic cell capable of expressing the cloned sequences. Importantly, since eukaryotic DNA may contain intervening sequences, and since such sequences cannot be correctly processed in prokaryotic cells, it is preferable to employ cDNA from a cell which is capable of expressing PTP-D in order .to produce a prokaryotic genomic expression vector library. Procedures for preparing cDNA and for producing a genomic library are disclosed by Sambrook et al (supra). A DNA sequence encoding a PTP-D protein or glycoprotein of the invention, or encoding a PTP-D protein or glycoprotein having amino acid deletions and/or insertions and/or substitutions of the invention, or encoding a chimeric molecule of the invention, may be recombined with vector DNA in accordance with conventional techniques, including blunt-ended or staggered-ended termini for ligation, restriction enzyme digestion to provide appropriate termini, filling in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and ligation with appropriate ligases. Techniques for such manipulations are disclosed by Sambrook et al. (supra), and are well known in the art. A nucleic acid construct, such as DNA, is said to be "capable of expressing" a polypeptide if it contains nucleotide sequences which contain transcriptional and translational regulatory information and such sequences are "operably linked" to nucleotide sequences which encode the polypeptide. An operable linkage is a linkage in which the regulatory DNA sequences and die DNA sequence sought to be expressed are connected in such a way as to permit gene expression. The precise nature of the regulatory regions needed for gene expression may vary from organism to organism, but shall in general include a promoter region which, in prokaryotes, contains both the promoter (which directs the initiation of RNA transcription) as well as the DNA sequences which, when transcribed into RNA, will signal the initiation of protein synthesis. Such regions will normally include those 5'-non-coding sequences involved with initiation of transcription and translation, such as the TATA box, capping sequence, CAAT sequence, and the like. If desired, the non-coding region 3' to the gene sequence coding for the protein may be obtained by the above-described methods. This region may be retained for its transcriptional termination regulatory sequences, such as termination and polyadenylation. Thus, by retaining the 3 '-region naturally contiguous to the DNA sequence coding for the protein, the transcriptional termination signals may be provided. Where the transcriptional termination signals are not satisfactorily functional in the expression host cell, then a 3' region functional in the host cell may be substituted. Two DNA sequences (such as a promoter region sequence and a PTPase-encoding sequence) are said to be operably. linked if the nature of the linkage between the two DNA sequences does not (1) result in the introduction of a frame-shift mutation, (2) interfere with the ability of the promoter region sequence to direct the transcription of the PTP-D gene sequence, or (3) interfere with the ability of the PTP-D gene sequence to be transcribed by die promoter region sequence. A promoter region would be operably linked to a DNA sequence if the promoter were capable of effecting transcription of that DNA sequence. Thus, to express die protein, transcriptional and translational signals recognized by an appropriate host are necessary. A promoter is a double-stranded DNA or RNA molecule which is capable of binding RNA polymerase and promoting the transcription of an "operably linked" nucleic acid sequence. As used herein, a "promoter sequence" is the sequence of the promoter which is found on that strand of the DNA or RNA which is transcribed by the RNA polymerase. A "promoter sequence complement" is a nucleic acid molecule whose sequence is the complement of a "promoter sequence." Hence, upon extension of a primer DNA or RNA adjacent to a single-stranded "promoter sequence complement" or, of a "promoter sequence," a double-stranded molecule is created which will contain a functional promoter, if that extension proceeds towards the "promoter sequence" or the "promoter sequence complement. " This functional promoter will direct the transcription of a nucleic acid molecule which is operably linked to that strand of the double-stranded molecule which contains the "promoter sequence" (and not that strand of the molecule which contains the "promoter sequence complement"). Certain RNA polymerases exhibit a high specificity for such promoters. The RNA polymerases of the bacteriophages T7, T3, and SP-6 are especially well characterized, and exhibit high promoter specificity. The promoter sequences which are specific for each of these RNA polymerases also direct the polymerase to utilize (i.e. transcribe) only one strand of the two strands of a duplex DNA template. The selection of which strand is transcribed is determined by the orientation of the promoter sequence. This selection determines the direction of transcription since RNA is only polymerized enzymatically by the addition of a nucleotide 5' phosphate to a 3' hydroxyl terminus. Two sequences of a nucleic acid molecule are said to be "operably linked" when they are linked to each other in a manner which eitiier permits both sequences to be transcribed onto the same RNA transcript, or permits an RNA transcript, begun in one sequence to be extended into the second sequence. Thus, two sequences, such as a promoter sequence and any otiier "second" sequence of DNA or RNA are operably linked if transcription commencing in the promoter sequence will produce an RNA transcript of die operably linked second sequence. In order to be "operably linked" it is not necessary that two sequences be immediately adjacent to one another. Thus, as indicated above, in order to function as a promoter, a promoter sequence must be present as a double-stranded molecule. For the purposes of the present invention, the two strands of a functional promoter sequence are referred to as a "transcript" strand and a "complementary" strand. The "transcript" strand is that strand of the duplex which will be transcribed by the RNA polymerase (i.e. which serves as the template for transcription). The "complementary" strand is the strand which has a sequence complementary to the "transcript" strand, and which must be present, and hybridized to the "transcript" strand, in order for transcription to occur. Thus, when the "transcript" strand of a promoter sequence is operably linked to a second sequence, hybridization of the "transcript" strand with the "complement" strand, will, in the presence of a polymerase, result in the transcription of die "transcript" strand, and will produce an RNA transcript using the sequence of the "transcript" strand as a template. The promoter sequences of the present invention may be either prokaryotic, eukaryotic or viral. Suitable promoters are repressible, or, more preferably, constitutive. Examples of suitable prokaryotic promoters include promoters capable or recognizing the T4 (Malik et al. , J. Biol. Chem. 265: 1174-1181 (1984); Rosenberg et al, Gene 59:191-200 (1987); Shinedling et al, J. Molec. Biol. 795:471-480 (1987); Hu et al, Gene 42:21-30 (1986)), T3, Sp6, and T7 (Chamberlin et al Nature 228:221 -231 (1970); Bailey et al, Proc. Natl Acad. Sci. (U.S.A.) 50:2814-2818 (1983); Davanlook et al., Proc. Natl Acad. Sci. (U.S.A.) 57:2035-2039 (1984)) polymerases; the P R and P L promoters of bacteriophage lambda (The Bacteriophage Lambda, Hershey, A.D., Ed., Cold Spring Harbor Press, Cold Spring Harbor, NY (1973); Lambda II, Hendrix, R.W., Ed., Cold Spring Harbor Press, Cold Spring Harbor, NY (1980)); the trp, recA, heat shock, and lacZ promoters of E. coli; the α-amylase (Ulmanen et al, J. Bateriol 762:176-182 (1985)) and the ς-28- specific promoters of B. subtilis (Gilman et al., Gene 52: 11-20 (1984)); the promoters of the bacteriophages of Bacillus (Gryczan, T.J., In: The Molecular Biology of the Bacilli, Academic Press, Inc., NY (1982)); Streptomyces promoters (Ward et al, Mol Gen. Genet. 205:468-478 (1986)); the int promoter of bacteriophage lambda; the bla promoter of the 0-lactamase gene of pBR322, and the CAT promoter of die chloramphenicol acetyl transferase gene of pPR325, etc. Prokaryotic promoters are reviewed by Glick, B.R. (J. Ind. Microbiol. 7:277-282 (2987)); Cenatiempo, Y. (Biochimie 65:505-516 (1986)); Watson et al (In: Molecular Biology of the Gene, Fouπh Edition, Benjamin Cummins, Menlo Park, CA (1987)); and Gottesman, S. (Ann. Rev. Genet. 75:415-442) (1984)). Preferred eukaryotic promoters include the promoter of the mouse metallothionein I gene (Hamer et al , J. Mol Appl. Gen. 7:273-288 (1982)); the SV40 early promoter (Benoist et al , Nature (London) 290:304-310 (1981)); and the yeast gal4 gene promoter (Johnston et al , Proc. Natl Acad. Sci (USA) 79:6971-6975 (1982); Silver et al , Proc. Natl Acad. Sci. (USA) 57:5951-5955 (1984)). All of the above listed references are incorporated by reference herein. Strong promoters are preferred. Examples of such preferred promoters are those which recognize the T3, SP6 and T7 polymerases, the P L promoter of the mouse metallothionein I gene. A most preferred promoter for eukaryotic expression of PTP-D is SV40 promoter such as that driving transcription in the pLSV vector (Livneh et al, (1986) J. Biol Chem. 261, 12490-12497). The sequences of such polymerase recognition sites are disclosed by Watson et al. (In: Molecular Biology of the Gene, Fourth Edition, Benjamin/Cummings Publishing Co., Inc., Menlo Park, CA, (1987)). In a further aspect, the present invention relates to an antibody which is capable of specifically recognizing a PTP-D protein or glycoprotein or of specifically recognizing an epitope of a PTP-D protein or glycoprotein. The recombinantly expressed or naturally occurring PTP-D protein or glycoprotein, and/or the antibodies recognizing the PTP-D protein or glycoprotein may be used in a method of diagnosing diseases or conditions with abnormal expression or activation of PTP-D protein or glycoproteins. The present invention provides methods for evaluating the presence and die level of normal or mutant PTP-D protein or glycoprotein in a subject. Absence, or more typically, low expression of the PTP-D protein or glycoprotein, or presence of a mutant PTP-D protein or glycoprotein, in an individual may serve as an important predictor of susceptibility to oncogenic transformation and the development of cancer. Alternatively, over-expression of a PTP-D protein or glycoprotein,, possibly due to a mutant receptor/enzyme system insensitive to negative regulation, or due to overabundance of a stimulatory ligand in the body, may serve as an important predictor of susceptibility to diabetes. The invention is also directed to die use of such antibodies to detect the presence of, or measure the quantity or concentration of, a PTP-D protein or glycoprotein in a cell, a cell or tissue extract, or a biological fluid. In one aspect, the present invention relates to a method for detecting the presence of or measuring the quantity of a PTP-D protein or glycoprotein in a cell, comprising: (a) contacting said cell or an extract thereof with an antibody specific for an epitope of a PTP-D protein or glycoprotein; and (b) detecting the binding of said antibody to said cell or extract thereof, or measuring the quantity of antibody bound, thereby determining the presence of or measuring the quantity of said PTP-D protein or glycoprotein. The term "antibody" is meant to include polyclonal antibodies, monoclonal antibodies (mAbs), chimeric antibodies, and anti-idiotypic (anti-Id) antibodies. Polyclonal antibodies are heterogeneous populations of antibody molecules derived from die sera of animals immunized with an antigen. Monoclonal antibodies (mAbs) are a substantially homogeneous population of antibodies to specific antigens. MAbs may be obtained by methods known to tiiose skilled in die art. See, for example, Kohler et αl., Nature 256:495-497 (1975) and U.S. Patent No. 4,376,110. Such antibodies may be of any immunoglobulin class including IgG, IgM, IgE, IgA, GILD and any subclass thereof. The hybridoma producing the mAbs of this invention may be cultivated in vitro or in vivo. Production of high titers of mAbs in vivo production makes this the presently preferred method of production. Briefly, cells from the individual hybridomas are injected intraperitoneally into pristane-primed BALB/c mice to produce ascites fluid containing high concentrations of the desired mAbs. MAbs of isotype IgM or IgG may be purified from such ascites fluids, or from culture supernatants, using column chromatography methods well known to those of skill in the aπ. Chimeric antibodies are molecules in which different poπions are derived from different animal species, such as those having variable region derived from a murine MAb and a human immunoglobulin constant region. Chimeric antibodies and methods for their production are known in the aπ (Cabilly et al, Proc. Natl. Acad. Sci. USA 77:3273-3277 (1984); Morrison et al , Proc. Natl Acad. Sci. USA 57:6851-6855 (1984); Boulianne et al, Nature 572:643-646 (1984); Cabilly et al, European Patent Application 125023 (published November 14, 1984); Neuberger et al, Nature 574:268- 270 (1985); Taniguchi et al , European Patent Application 171496 (published February 19, 1985); Morrison et al, European Patent Application 173494 (published March 5, 1986); Neuberger et al, PCT Application WO 86/01533 (published March 13, 1986); Kudo et al, European Patent Application 184187 (published June 11 , 1986); Sahagan et al., J. Immunol. 757:1066-1074 (1986); Robinson et al , International Patent Publication #PCT/US86/02269 (published May 7, 1987); Liu et al , Proc. Natl. Acad. Sci. USA 54:3439-3443 (1987); Sun et al, Proc. Natl. Acad. Sci. USA 54:214-218 (1987); Better et al., Science 140: 1041-1043 (1988)). These documents are hereby incorporated by reference. An anti-idiotypic (anti-Id) antibody is an antibody which recognizes unique determinants generally associated with the antigen-binding site of an antibody. An anti-Id antibody can be prepared by immunizing an animal of the same species and genetic type (e.g. mouse strain) as the source of the mAb with the mAb to which an anti-Id is being prepared. The immunized animal will recognize and respond to me idiotypic determinants of die immunizing antibody by producing an antibody to these idiotypic determinants (the anti-Id antibody). The anti-Id antibody may also be used as an "immunogen" to induce an immune response in yet another animal, producing a so-called anti-anti-ld antibody. The anti-anti-ld may be epitopically identical to the original mAb which induced the anti-Id. Thus, by using antibodies to the idiotypic determinants of a mAb, it is possible to identify other clones expressing antibodies of identical specificity. Accordingly, mAbs generated against a PTP-D protein or glycoprotein of the present invention may be used to induce anti-Id antibodies in suitable animals, such as BALB/c mice. Spleen cells from such immunized mice are used to produce anti-Id hybridomas secreting anti-Id mAbs. Further, the anti- Id mAbs can be coupled to a carrier such as keyhole limpet hemocyanin (KLH) and used to immunize additional BALB/c mice. Sera from these mice will contain anti-anti-ld antibodies that have the binding propeπies of the original mAb specific for a PTP-D epitope. The anti-Id mAbs thus have their own idiotypic epitopes, or"idiotopes" structurally similar to the epitope being evaluated, such as a PTP-D protein or glycoprotein. - The term "antibody" is also meant to include both intact molecules as well as fragments thereof, such as, for example, Fab and F(ab') 2 , which are capable of binding antigen. Fab and F(ab') 2 fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding than an intact antibody (Wahl et al, J. Nucl Med. 24:316-325 (1983)). It will be appreciated that Fab and F(ab') 2 and other fragments of the antibodies useful in the present invention may be used for the detection and quantitation of a PTP-D protein or glycoprotein according to the methods disclosed herein for intact antibody molecules. Such fragments are typically produced by proteoJytic' cleavage, using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab') 2 fragments). The antibodies, or fragments of antibodies, useful in the present invention may be used to quantitatively or qualitatively detect the presence of cells which express a PTP-D protein or glycoprotein. This can be accomplished by immunofluorescence techniques employing a fluorescently labeled antibody (see below) coupled with light microscopic, flow cytometric, or fluori metric detection. The antibodies (or fragments thereof) useful in the present invention may be employed histologically, as in immunofluorescence or immunoelectron microscopy, for in situ detection of a PTP-D protein or glycoprotein. In situ detection may be accomplished by removing a histological specimen from a patient, and providing the labeled antibody of the present invention to such a specimen. The antibody (or fragment) is preferably provided by applying or by overlaying the labeled antibody (or fragment) to a biological sample. Through the use of such a procedure, it is possible to determine not only the presence of a PTP-D protein or glycoprotein but also its distribution on the examined tissue. Using the present invention, those of ordinary skill will readily perceive that any of a wide variety of histological methods (such as staining procedures) can be modified in order to achieve such in situ detection. Such assays for a PTP-D protein or glycoprotein typically comprise incubating a biological sample, such as a biological fluid, a tissue extract, freshly harvested cells such as lymphocytes or leukocytes, or cells which have been incubated in tissue culture, in the presence of a detectably labeled antibody capable of identifying a PTP-D protein or glycoprotein, and detecting the antibody by any of a number of techniques well-known in the art. The biological sample may be treated with a solid phase suppoπ such as nitrocellulose, or other solid suppoπ which is capable of immobilizing cells, cell paπicles or soluble proteins. The suppoπ may then be washed with suitable buffers followed by treatment with the detectably labeled PTP-D specific antibody. The solid phase suppoπ may then be washed with die buffer a second time to remove unbound antibody. The amount of bound label on said solid suppoπ may then be detected by conventional means. By "solid phase suppoπ" is intended any suppoπ capable of binding antigen or antibodies. Well-known supports, or carriers, include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamides, gabbros, and magnetitite. The nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention. The suppoπ material may have viπually any possible structural configuration so long as the coupled molecule is capable of binding to an antigen or antibody. Thus, the suppoπ configuration may be spherical, as in a bead, or cylindrical, as in the inside surface of a test tube, or the external surface of a rod. Alternatively, the surface may be flat such as a sheet, test strip, etc. Preferred supports include polystyrene beads. Those skilled in the art will know many other suitable carriers for binding antibody or antigen, or will be able to ascertain the same by use of routine experimentation. The binding activity of a given lot of anti-PTP-D antibody may be determined according to well known methods. Those skilled in the art will be able to determine operative and optimal assay conditions for each determination by employing routine experimentation. Other steps as washing, stirring, shaking, filtering and die like may be added to the assays as is customary or necessary for the particular situation. One of the ways in which the PTP-D-specific antibody can be detectably labeled is by linking the same to an enzyme and use in an enzyme immunoassay (EIA). This enzyme, in turn, when later exposed to an appropriate substrate, will react with the substrate in such a manner as to produce a chemical moiety which can be detected, for example, by spectrophotometnc, fiuorimetric or by visual means. Enzymes which can be used to detectably label the antibody include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. The detection can be accomplished by colorimetric methods which employ a chromogenic substrate for the enzyme. Detection may also be accomplished by visual comparison of the extent of enzymatic reaction of a substrate in comparison with similarly prepared standards. Detection may be accomplished using any of a variety of other immunoassays. For example, by radioactively labeling the antibodies or antibody fragments, it is possible to detect a PTP-D protein or glycoprotein through the use of a radioimmunoassay (RIA) (see, for example, Work et al, Laboratory Techniques and Biochemistry in Molecular Biology, North Holland Publishing Company, New York, (1978), which is incorporated by reference herein). The radioactive isotope can be detected by such means as the use of a gamma counter or a scintillation counter or by autoradiography. It is also possible to label the antibody with a fluorescent compound. When the fluorescently labeled antibody is exposed to light of the proper wave length, its presence can then be detected due to fluorescence. Among the most commonly used fluorescent labeling compounds are fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde and fluorescamine. The antibody can also be detectably labeled using fluorescence emitting metals such as 152 Eu, or others of the lanthanide series. These metals can be attached to the antibody using such metal chelating groups as diethylenetriaminepentacetic acid (DTP A) or ethylenediaminetetraacetic acid (EDTA). The antibody also can be detectably labeled by coupling it to a chemiluminescent compound. The presence of the chemiluminescent-tagged antibody is then determined by detecting the presence of luminescence that arises during the course 1 of a chemical reaction. Examples of particularly useful chemiluminescent labeling compounds are luminol, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester. Likewise, a bioluminescent compound may be used to label the antibody of the present invention. Bioluminescence is a type of chemiluminescence found in biological systems in- which a catalytic protein increases the efficiency of the chemiluminescent reaction. The presence of a bioluminescent protein is determined by detecting the presence of luminescence. Important bioluminescent compounds for purposes of labeling are luciferin, luciferase and aeluorin. The present invention also relates to a metiiod for detecting die presence of a nucleic acid construct encoding a PTP-D protein or glycoprotein, or a nucleic acid construct encoding a mutant PTP-D protein or glycoprotein, in a subject, comprising: (a) contacting a cell or an extract thereof from said subject with an oligonucleotide probe encoding at least a poπion of said normal or mutant PTP-D protein or glycoprotein under hybridizing conditions; and (b) measuring the hybridization of said probe to the nucleic acid of said cell, thereby detecting the presence of said nucleic acid construct. The method may comprise an additional step (c) before step (a). Step (c) provides selectively amplifying the amount of nucleic acid of said cell encoding said PTP-D protein or glycoprotein, which may be by the polymerase chain reaction. Oligonucleotide probes encoding various poπions of PTP-D protein or glycoproteins (see above) are used to test cells from a subject for the presence of DNA or RNA sequence encoding a PTP-D protein or glycoprotein. Techniques for synthesizing such probes are disclosed by for example, Wu et al., Prog. Nucl Acid. Res. Molec. Biol 27:101-141 (1978). A preferred probe would be one directed to the nucleic acid sequence encoding at least four amino acid residues, and preferably at least five amino acid residues, of a PTP-D protein or glycoprotein of the present invention (see Example 4 below). Qualitative or quantitative assays can be performed using such probes. For example, Noπhern analysis (see Example 3 below) is used to measure expression of a PTP-D mRNA, such as PTP-D1 mRNA and PTP-D2 mRNA, in a cell or tissue preparation. Such methods can be used even with very small amounts of DNA obtained from an individual, following use of selective amplification techniques. Recombinant DNA methodologies capable of amplifying purified nucleic acid fragments have long been recognized. Typically, such methodologies involve the introduction of the nucleic acid fragment into a DNA or RNA vector, the clonal amplification of the vector, and the recovery of the amplified nucleic acid fragment. Examples of such methodologies are provided by Cohen et al (U.S. Patent No. 4,237,224); and Sambrook et al, (supra), which documents are herein incorporated by reference.) Recently, an in vitro, enzymatic method has been described which is capable of increasing the concentration of such desired nucleic acid molecules. This method has been referred to as the "polymerase chain reaction" or "PCR" (Mullis et al, Cold Spring Harbor Symp. Quant. Biol 57:263-273 (1986); Erlich, EP 50,424; EP 84,796, EP 258,017, EP 237,362; Mullis, K., EP 201,184; Mullis et al, U.S. 4,683,202; Erlich, H., U.S. 4,582,788; and Saiki et al, U.S. 4,683,194). The present invention also relates to a method for identifying in a chemical or biological preparation a compound capable of binding to a PTP-D protein or glycoprotein, said method comprising: (a) attaching said PTP-D protein or glycoprotein or a compound-binding portion thereof to a solid phase matrix; (b) contacting said chemical or biological preparation with said solid phase matrix allowing said compound to bind, and washing away any unbound material; and (c) detecting the presence of said compound bound to said solid phase. The present invention also relates to a method for isolating from a complex mixture a compound capable of binding to a PTP-D protein or glycoprotein, comprising: (a) attaching said PTP-D protein or glycoprotein, or a compound-binding portion thereof, to a solid phase matrix; (b) contacting said complex mixture with said solid phase matrix allowing said compound to bind, and washing away any unbound material; and (c) eluting said bound compound, thereby isolating said compound. By "compound capable of binding to a PTP-D protein or glycoprotein" is meant a naturally occurring or synthetically produced molecule which interacts with PTP-D outside of the catalytic site of the phosphatase domain. By the "catalytic site" is meant the smallest, contiguous part of PTP-D which contains phosphatase activity. Such compounds may directly or indirectly modulate the enzymatic activity of the PTP-D protein or glycoprotein. Examples of such compounds are (i) intracellular proteins which interact with and may be dephosphorylated by a PTP-D protein or glycoprotein; (ii) naturally occurring molecules produced by other cell types. By a "compound-binding portion" of a PTP-D protein or glycoprotein is meant a part of the molecule which is outside of the catalytic site. Any part of the PTP-D proteins or glycoproteins which are not part of the catalytic site may be a compound-binding portion. A "compound-binding portion" may be prepared from naturally occurring or recombinantly expressed PTP-D proteins or glycoproteins by proteolytical cleavage followed by conventional purification procedures known to those of skill in the art. Alternatively, the compound-binding poπion of a PTP-D protein or glycoprotein may be produced by recombinant technology known to tiiose of skill in the aπ by expressing only these parts of PTP-D in suitable cells. In a still further aspect, the present invention relates to a method of screening for antagonists which are defined as molecules which directly or indirectly inhibit the enzymatic activity or activation of a PTP-D protein or glycoprotein. In a fuπher aspect, the present invention relates to a method of screening for agonists which are defined as molecules which directly or indirectly increase the enzymatic activity or activation of a PTP-D protein or glycoprotein. PTP-D proteins or glycoproteins of the present invention are useful in methods for screening drugs and other agents which are capable of activating or inhibiting the phosphatase activity, and thereby affecting major pathways of cellular metabolism. By attaching an intact PTP-D protein or glycoprotein or a fragment of a PTP-D protein or glycoprotein, to a solid phase matrix, an affinity probe is created which can be used to screen biological products or chemical agents for their capacity to interact with a PTP-D protein or glycoprotein on the basis of their binding activity. Bound material can then be eluted from the affinity probe in purified form. A PTP-D protein or glycoprotein, or a PTP-D protein or glycoprotein having amino acid deletions and/or inseπions and/or substitutions and having enzymatic activity can be used for testing of compounds capable of enhancing or inhibiting the phosphatase activity. The ability of a compound under test to modify phosphatase activity can be tested in an in vitro system wherein the test compound is added to a purified PTP-D protein or glycoprotein, or to a PTP-D protein or glycoprotein having amino acid deletions and/or inseπions and/or substitutions and having enzymatic activity, and the effects on enzyme activity measured using standard enzymological procedures well known to those of skill in the art. A suitable fragment of a PTP-D protein or glycoprotein for use in screening may be prepared by limited proteolytic treatment of the naturally occurring or recombinantly expressed PTP-D protein or glycoprotein. Alternatively, suitable fragment(s) of PTP-D may be produced by recombinant technology. As an example, which is not intended to be in any way limiting to the scope of the invention claimed, it may be preferable to use only the catalytic domains for screening purposes. Such catalytic domains, which consist only of the minimum number of amino acids needed for enzymatic activity, could be produced either alone or as paπ of a fusion protein in suitable hosts (e.g., E. colϊ) by recombinant technology well known to those of skill in the art. Alternatively, the action of a compound on PTPase activity can be measured in a whole cell preparation using live or fixed cells, or a membrane fraction derived from live or fixed cells. This method is useful for screening compounds acting directly on the enzymatic portion of a PTP-D protein or glycoprotein. If a PTP-D molecule or glycoprotein has an extracellular receptor portion, then this method is useful for screening compounds acting via the extracellular receptor portion. A test compound is incubated with cells, or with a membrane preparation derived therefrom, which express high amounts of a PTP-D protein or glycoprotein of this invention, such as transfected COS or NIH-3T3 cells. The amount of cellular phosphotyrosine is then measured, using methods well-known in the art (Honegger, et al, Cell 57: 199-209 (1987); Margolis et al, Cell 57: 1101-1107 (1989)). The results are compared to results obtained in die absence of the test compound, or in me absence or presence of a known activator of a PTP-D protein or glycoprotein. In such studies, the action of the test compound in the presence of an activator of tyrosine kinase can also be measured. A compound which stimulates PTPase activity will result in a net decrease in the amount of phosphotyrosine, whereas a compound which inhibits PTPase activity will result in a net increase in the amount of phosphotyrosine. In the case of growth factor receptors which are tyrosine kinases, such as the receptors for epidermal growth factor (EGF) and for platelet-derived growth factor (PDGF), tyrosine phosphorylation is linked to cell growth and to oncogenic transformation. Activation of a PTPases, leading to dephosphorylation, would serve as a counterregulatory mechanism to prevent or inhibit growth, and might serve as an endogenous regulatory mechanism against cancer. Thus, mutation or dysregulation of this receptor. enzyme system may promote susceptibility to cancer. The insulin receptor is also a tyrosine kinase, and phosphorylation of tyrosine in cells bearing insulin receptors would be associated with normal physiological function. In contrast to the case of cell growth and cancer, activation of a PTPase would counteract insulin effects. Subnormal PTPase levels or enzymatic activity would act to remove a normal counterregulatory mechanism. Perhaps more important, though, over-activity, or inappropriate activation, of a PTPase would be expected to inhibit or totally prevent the action of insulin on cells, leading to diabetes (of an insulin-resistant variety). Thus, susceptibility to diabetes may be associated with PTPase dysregulation. Therefore, the methods of die present invention for identifying normal or mutant PTP-D genes, or for measuring the umount or activity of PTP-D protein or glycoprotein associated with a cell or tissue, can serve as methods for identifying susceptibility to cancer, diabetes, or other diseases associated with alterations in cellular phosphotyrosine metabolism. The invention also relates to the use of such identified antagonists or agonists in pharmaceutical compositions intended for treatment of diseases or conditions with either normal or abnormal expression of a PTP-D protein or glycoprotein. The composition may typically be in a form for systemic or topical injection or infusion and may, as such, be formulated with a suitable carrier for injection or infusion. The present invention also relates to a method for preventing or treating diseases or conditions involving the activation of a PTP-D protein or glycoprotein, the method comprising administering, to a patient in need thereof, an effective dosage of a PTP-D protein or glycoprotein of the invention or an antibody of the invention or a molecule that stimulates or inhibits enzymatic activity of a PTP-D protein or glycoprotein of the invention. The present invention is further illustrated in the examples shown below which are not intended to be in any way limiting to the scope of the invention as claimed. EXAMPLE 1 Identification of a New PTPase Subfamily Using the Polymerase Chain Reaction (PCR) Total RNA was isolated from human skeletal muscle by the guanidinium thiocyanate/CsCl procedure (Chirgwin et al, Biochem. 75:5293- 5299 (1979)). Poly(A) + RNA was isolated on an oligo(dT) cellulose column (Aviv et al, Proc. Natl. Acad. Sci. USA 55: 1408-1412 (1972)). First strand cDNA was synthesized from 2 μg poly(A) + using ligo(dT) priming and Moloney Murine Leukemia Virus RNase H " Reverse Transcriptase from Gibco BRL (Gaithersburg, MD 20877, U.S.A.) in accordance with the manufacturer's recommendations. cDNA corresponding to PTPases expressed in skeletal muscle were isolated by the polymerase chain reaction (Saiki et al, Science 259:487-491 (1988)). In short, human muscle first strand cDNA from above (corresponding to about 50 ng) was amplified with the following set of degenerative oligonucleotide primers using me Gene Amp kit (Perkin Elmer Cetus, Norwalk, CT, U.S.A.). Sense pήme (oligonucleotide no. 58) 5 * A(CT)TT(CT)TGG(ACGKAG)(AG)ATG(AG)T(TCGA)TGG 3' [SEQ. ID NO. 10] Anti-sense primer (oligonucleotide no. 57) 5' CC(TCGA)A(CT)(AGT)CC(ATC)GC(AG)CT(GA)CAGTG 3' [SEQ. ID NO. 11] The primers correspond to the following amino acid consensus sequences: •, Sense primer (oligonucleotide #58) F W X M X W [SEQ. ID NO. 12] Antisense primer (oligonucleotide #57) H C S A G ( S / I / V ) G. [SEQ. ID NO. 13] Each PCR cycle comprise a denaturation step at 94°C for 1 minute, an annealing step at 37°C for 2 minutes, and an extension step at 72°C for 2 minutes. Thirty to 40 cycles were carried out. The reaction products were subjected to agarose gel electrophoresis. The fragments of the expected size (based on the structure of already described PTPases) were isolated, subcloned using the TA cloning system (Invitrogen, San Diego, California) and sequenced by the enzymatic chain termination method described by Sanger et al, Proc. Natl Acad. Sci. USA 74:5463-5467 (1977)), (Sequenase, U.S. Biochemicals) using standard techniques (as described in Current Protocols in Molecular Biology, eds. F.M. Ausubel et al, John Wiley & Sons, New York, 1988). The paπial DNA sequence and the deduced amino acid sequence of two PCR fragments, termed PTP-D 1 and PTP-D2, are shown in Figure 1 and Figure 2, respectively. The deduced amino acid sequences were compared with PTPase IB in Figure 3 A using the CLUSTAL program (Higgins, C, Fuch, R., and Bleasby, D., Multiple Sequence Alignment; CABIOS (1991) (in press)). It appears that both fragments are clearly homologous to other known PTPases, but, surprisingly, have features not yet described for this class of enzymes (analysis by the University of Wisconsin, Genetics Computer Group program). These unique features of PTP-D 1 and PTP-D2 are shown below in comparison with the consensus sequences of the previously described known PTPases (differences are underlined): 1. PTP-D 1/D2 S X X Y W P [SEQ. ID NO. 6] Consensus C X X Y W P [SEQ. ID NO. 2] 2. PTP-D 1/D2 I A M V X X X X E [SEQ. ID NO. 7] Consensus (I/V/L) V (M/I/L) (V/L/I/M) X X X X E [SEQ. ID NO. 9] EXAMPLE 2 cDNA Cloning of a Member of the PTP-D Subfamily mRNA was prepared from human skeletal muscle as described in EXAMPLE 1. A cDNA library was constructed using the methods described by Okayama and Berg, Mol Cell Biol 2: 161-170 (1982); Okayama and Berg, Mol Cell Biol. 5:280-289 (1983). The pCDVI-PL vector was used for preparation of the primer fragment (Noma et al, Nature 579:640-646 (1986). A shoπ synthetic adapter was used as second strand primer as recently described (Boel et al, BioTechniques 77:XX (1991)). E. coli DH5α (Gibco BRL, Gaithersburg, MD 20877, U.S.A.) was used for transformation according to the protocols by H. Inuoue et al, Gene 96:23-28 (1990). After transformation, the cells were plated onto LB plates (containing 50 μg ampicillin/ml) at a density of 15,000-20,000 colonies per plate. Nitrocellulose replica filters (Scleicher & Schuell, BA85) were screened with standard colony hybridization technique ((Maniatis et al., Molecular Cloning (A Laboratory Manual), Cold Spring Harbor Laboratory, second edition (1988). The following oligonucleotide was synthesized, labeled at the 5' end using T 4 polynucleotide kinase and [7- 32 P]ATP (Amersham) and used for screening of the cDNA library: 5' ATA GCA ATG GTG ACA GCA GAA 3' ISEQ. ID NO. HI This oligonucleotide corresponds to the amino acid sequence Ile-Ala- Met-Val-Thr-Ala-Glu of the PCR fragment no. 1 from EXAMPLE 1. Ten pmoles of the labeled oligonucleotide in 50 ml of hybridization solution (6 x SSC, 5x Denhardt's solution, 0.05 % SDS (Current Protocols in Molecular Biology, eds. F.M. Ausubel et al, John Wiley & Sons, New York, (1988)) were added to replica nitrocellulose filters and allowed to hybridize at 42 °C for 3 hours. Then the filters were washed in 6 x SSC, 0.05 % SDS three times at room temperature, once at 42°C and finally once at 48°C. Positive colonies identified by autoradiography were isolated by standard techniques ((Maniatis et al, Molecular Cloning (A Laboratory Manual), Cold Spring Harbor Laboratory, second edition (1988)). The paπial sequence of one positive clone, denoted PTP-D 1, and the deduced amino acid sequence is shown in Figure 4. This paπial sequence includes the sequence of the PCR fragment no. 1 from above and thus confirms the identity of the isolated cDNA clone. Further, comparison with previously described PTPases indicates at least one additional unique feature of PTP-D 1 (the difference is underlined): 3. PTP-D1 G Y I N A S [SEQ. ID NO. 5] Consensus N/D Y I N A S/N [SEQ. ID NO. 4] EXAMPLE 3 Northern Blot Analysis of PTP-D1 and PTP-D2 Total RNA was isolated from human skeletal muscle by the acid guanidium thiocyanate-phenol-chloroform extraction procedure as described by Puissant et al, BioTechniques 5: 148-149 (1990)). Poly(A) + RNA was isolated on an oligo(dT) column (Aviv et al, Proc. Natl Acad. Sci. USA 69:1408-1412 (1972)). Fifteen μg poly(A) + RNA were loaded in the lane probed for PTP-D1 expression, and 7.5 μg were loaded in the lane analyzed for PTP-D2 expression, the RNA was separated in an agarose-formaldehyde gel and blotted to nitrocellulose filters using standard techniques (Current Protocols in Molecular Biology, eds. F.M. Ausubel et al, John Wiley & Sons, New York (1988)). The filters were hybridized with 32 P-labeled cDNA fragments corresponding to the sequences shown for PTP-D 1 and PTP-D2. The 32 P-labeling was done with the Random Primers DNA Labeling System (Cat. no. 8187SA, Bethesda Research Laboratories, Gaithersburg, MD 20877, U.S.A.) according to the manufacturer's instructions. Subsequently, the filters were applied to X-ray films. An analysis of the Noπhern Blot shows that the major transcripts of PTP-D 1 and PTP-D2 in skeletal muscle were 6.5 kb and 11 kb, respectively. EXAMPLE 4 Identification of New Members of the PTP-D Subfamily Total RNA is isolated from each of the following tissues and cell lines: skeletal muscle, liver, placenta, Hep G2 (American Type Culture Collection (ATCC) HB8065), RD (ATCC CCL 136) (Puissant et al, BioTechniques 5: 148-149 (1990)). Poly(A) + RNA is isolated on an oligo (dT) column (Aviv et al , Proc. Natl. Acad. Sci. USA 69: 1408-1412 (1972)). First strand cDNA synthesis is performed as described in Example 1. The cDNA preparations from the above-mentioned tissues and cell lines are individually subjected to the polymerase chain reaction using standard conditions (P R Technology - Principles and Applications for DNA Amplification, Erlich, H.E., ed., Stockton Press, New York, (1989)). The following primers are used for the amplifications: Sense primer: (oligonucleotide no. 58, see Example 1 of the present invention) in combination with either of the two anti-sense primers: Oligonucleotide no. 250 (corresponding to * the amino acid sequence CYATTG [SEQ. ID NO. 15] of PTP-D 1 and PTP-D2): C 5' AG(TCGA)CC(TCGA)GT CGA)GT(TCGA)GC(AG)TA(AG)CA < [SEQ. ID NO. 16] Oligonucleotide no. 251 (corresponding to the amino acid sequence QERTVW [SEQ. ID NO. 17] of PTP-D1): 5 ' GGT(TCG A) AC(TCGA)GT(TCG A)C(TG)(TC)TC(TC)T [SEQ. ID NO. 18] Thiπy to 40 PCR cycles are carried out. The reaction products are subjected to agarose gel electrophoresis. The fragments of die expected size (around 190 bp for the combination of oligonucleotides nos. 58 and 250; around 235 bp for the combination of oligonucleotides nos. 58 and 251) are isolated, blunt-ended and subcloned into the pGEM3 vector (Promega) using standard techniques (Ausubel et al, Current Protocols in Molecular Biology, John Wiley & Sons, New York, (1988)). The subcloned PCR products are sequenced by the enzymatic chain termination method (Sanger et al , Proc. Natl. Acad. Sci. USA 74:5463-5467 (1977)) using Sequenase (United States Biochemical, Cleveland, Ohio 44122, U.S.A.). The nucleotide sequences and the corresponding amino acid sequences are compared to d e sequences of PTP-D 1 and PTP-D2. Clones which exhibit 70% or more identity to PTP- DJ/PTP-D2 and/or the PTP-D 1/D2 sequences shown in Examples 1 and 2 are identified as members of the PTP-D subfamily according to the present invention. EXAMPLE 5 Detection of the Presence of a Nucleic Acid for a PTP-D Protein Total RNA is isolated- from the cell lines Hep G2 (American Type Culture Collection (ATCC) HB8065) and RD (ATCC CCL 136) (Puissant et al, Biotechniques 8:148-149 (1990)). Poly(A) + RNA is isolated on an oligo(dT) column (Aviv & Leder, Proc. Natl. Acad. Sci. USA 69: 1408-1412 (1972)). First strand cDNA synthesis is performed as described in Example I. The cDNA is subjected to the polymerase chain reaction using standard conditions (PCR Technology - Principles and Applications for DNA Amplification, Eriich, H.E. ed., Stockton Press, New York (1989)). The following primers are used for the amplifications: Sense primer: 5' ATAGCAATGGTGACAGCAGAA 3' [SEQ. ID NO. 19] Anti-sense pή er: 5 ' CGCCC( A/G) A(C/T)(T/C/G/A)CC(T/C/G/ A)GC /C/G/A)CT (G/A)CAGTG [SEQ. ID NO. 20] 3' Thirty-five cycles are carried out. The reaction products are subjected to agarose gel electrophoresis. The fragments of die expected size (360 bp) are isolated, blunt-ended and subcloned into the pGEM3 vector (Promega) using standard techniques (Ausubel et al, Current Protocols in Molecular Biology, John Wiley & Sons, New York (1988)). The PTP-D identity of the subcloned PCR fragments is verified by sequencing using the enzymatic chain termination method (Saπger et al. , Proc. Natl Acad. Sci. USA 74:5463-5467 (1977)) using Sequenase (United States Biochemical, Cleveland, Ohio 44122, U.S.A.). EXAMPLE 6 Detection of the Presence of and Measurement of the Quantity of a PTP-D Protein or Glycoprotein in a Cell Change of the prokarvotic expression vector pGEX To accommodate a cDNA fragment from PTP DI (see below) the cloning sites of the pGEX2T vector (Pharmacia, Uppsala, Sweden) is changed using standard techniques (Current Protocols in Molecular Biology, eds. F.M. Ausubel et al, John Wiley & Sons, New York, 1988). The pGEX2T vector is digested with the restriction enzymes BamHl and EcøRI and isolated. The following oligonucleotides are ligated into d e digested pGΕX2T vector. 5'GATCTCCGAATTCCATGGATCCAGGCCTCTAGAAGCTTAC 3 * [SEQ. ID NO. 21] 3' AGGCTTAAGGTACCTAGGTCCGGAGATCTTCGAATGTTAA 5' [SEQ. ID NO. 22] thereby giving rise to the vector pGEX-AK2 with the following cloning sites: 5' EcøRI, Ncøl, BamHl, Stul, Xbal, Hindlll 3' Expression of GST-PTP DI fusion protein in E. coli The cDΝA encoding PTP DI (EXAMPLE 2) is digested with die restriction enzymes EcøRI and BgUL After digestion, a fragment of about 1600 bp is isolated and ligated into the pGΕX-AK2 (digested witii EcøRI and BamHl) using standard techniques (Current Protocols in Molecular Biology, eds. F.M. Ausubel et al, John Wiley & Sons, New York, 1988). The inseπed fragment corresponds to the coding region of PTP DI shown in Figure 4 of the present invention (i.e., it is coding for 272 amino acids) and about 800 bp of the 3' untranslated region. The pGΕX-AK2/PTP DI vector construct, which encodes a fusion protein of glutathione S-transferase and PTP DI (Smith et al, Proc. Natl. Acad. Sci. USA 55:87-3-8707 (1988)), is introduced into the E. coli strains DH5α (Cat. No. 8263SA, Bethesda Research Laboratories, Gaithersburg, MD) and SURE™ (Cat. No. 200294, Stratagene, La Jolla, CA 92037). Overnight cultures of the transformed E. coli are grown in LB medium and diluted 1: 10 in fresh medium and grown for 1 hour. Isopropyl-l-thio-ø- D-galactopyranoside (IPTG) is added to a final concentration of 0.5 mM (DH5α) and 5 mM (SURE) and the cultures are incubated for a fuπher 4 hours. Controls: 1) pGEX-AK2 with and without IPTG; 2) pGEX-AK2/PTP DI without addition of IPTG. The GST-PTP DI fusion protein is isolated either as an insoluble product from inclusion bodies (using 3 washes in 50 mM N-2-Hydroxyethylpiperazine-N'-2-ethanesulphonic acid (HEPES) buffer pH 7.5 containing 1.0 percent (vol/vol) Triton X100) or as a soluble protein using glutathione-Sepharose 4B affinity chromatography (Cat. No. 17-0756-01, Pharmacia, Uppsala, Sweden) according to the manufacturer's instructions. Production of antibodies with specificity for PTP DI Antiserum witii specificity for PTP DI is produced by standard techniques (Practical Immunology 3rd Edition, L. Hudson & F.C. Hay, Blackwell, Oxford (1989)). lπ brief, 200 μg of the GST-PTP DI fusion protein in 200 μ\ phosphate buffered saline are combined with an equal volume of Freund's complete adjuvant (Sigma, Cat. No. F5881) and injected intramuscularly into die thigh muscle of two New Zealand rabbits. Each rabbit receives 100 μg of the fusion protein. Two weeks after the first injection, boost injections are performed (same procedure as the initial immunization but without Freund's adjuvant). After further two weeks 20 ml of blood are obtained from each rabbit. The blood is allowed to clot at room temperature for 1 hour in glass tubes, which are centrifuged after loosening the clot from the well of the tubes. The serum is transferred to a new tube and stored in aliquots at -20°C until use. To remove the antibodies which react with die glutathione S-transferase (GST) the serum is passed over a glutathione-Sepharose 4B column which has been saturated with glutathione S-transferase using the procedure described above ("Expression of GST-PTP DI fusion protein in E. coli). The pGEX- AK2 construct is used to produce the GST protein. The serum is passed three times over the column to ensure complete removal of the anti-GST antibodies. The efficiency of the removal is assessed by Western blotting as described below ("Detection of the Presence and Measurement of the Quantity of PTP- Dl in a Cell Line"). Detection of the Presence and Measurement of the Quantity of PTP-D 1 in a Cell Line The anti-PTP DI antibody can be used to detect the expression of PTP DI in mammalian cells. Immunofluorescence according to standard procedures will provide information abut expression in specific cell lines and tissues. Even more importantly, this antibody preparation can be used to determine the quantity in cell lines and tissues. As an example of the latter application of the anti-PTP DI antibody, the detection of PTP DI in the RD cell line (American Type Culture Collection CCL 136) is described below. It should be emphasized that this EXAMPLE should not in any way limit die use of the antibody which can be used for detection of PTP DI in otiier cells and tissues as well. Likewise, the antibody preparation can be useful in purification of PTP DI and for establishing other types of detection assays. Using standard techniques, die RD (embryonal rhabdomyosarcoma; human) cell line is cultured in minimum essential medium (Eagle; Cat. No. 041-022570, Gibco, Life Technologies Ltd., Paisley, Scotland) with twice the normal concentrations of amino acids and vitzmins with Hanks' balanced salt solution and 10 percent (v/v) fetal calf serum (Gibco-BRL). The cells are washed twice in phosphate ^ buffered saline and the supernatant removed. The cells from one 10 cm tissue culture plate are lysed in 800 μl of Triton X100 lysis buffer (20 mM HEPES pH 7.5, 50 M NaCl, 10 percent glycerol, 1.0 percent Triton X100, 1.5 mM MgCI 2 , 4 mM Ethylene SUBSTITUT Glycol-bis( 3-aminoethylethyl ether) N,N,N',N'-tetraacetate (EGTA; Sigma ED2SS), 10 / χg/ml aprotinin, 1 mM phenyl methylsulfonyl fluoride (PMSF)), centrifuged and the supernatant is stored in aliquots at -80°C until use. One to fifty μl of this lysate is mixed with 25 μl SDS sample buffer (62.5 mM Tris-Cl pH 7.0, 3.0 percent (w/v) SDS, 10 percent (v/v) glycerol, 10 percent 2-mercaptoethanol, and 0.05 percent (w/v) bromophenol blue), boiled for 5 minutes, separated by SDS-polyacrylamide gel electrophoresis (7.5 percent) and blotted onto nitrocellulose using standard techniques (Burnette, W.N. (1981) Anlyt. Biochem. 772:195-201). A standard curve for quantitative determination of PTP DI is produced by using defined amounts of the E. coli- produced GST-PTP DI fusion protein from above in parallel with the RD cell lysates. The nitrocellulose filters are incubated for 30 minutes with 2 grams milk powder (Carnation, Non fat dry milk, Carnation, Los Angeles) per liter phosphate buffered saline (PBS) to block unspecific binding, washed once in PBS containing 0.02 percent (v/v) Tween 20 (Sigma P1379) (PBS-Tween) and 0.2 percent (w/v) gelatin (BioRad Cat. No. 170-6537, Richmond, California), washed 3 times in PBS-Tween and finally incubated for 4 hours with a 1:200 dilution (in PBS-Tween) of die anti-PTP DI antibody preparation from above. After tiiree washings in PBS-Tween, the filters are incubated with horseradish peroxidase-conjugated goat anti-rabbit IgG (Cat. No. 170-6525, BioRad). The filters are washed three times in PBS-Tween and the amount of rabbit antibody, and thereby the amount of PTP DI, is determined by the enhanced chemiluminescence (ECL) technique according to the manufacturer's instructions (Cat. No. RPN 2106, Amersham, UK). By comparing the signals obtained from the RD cell line widi the standard curve obtained with the E. coli produced GST-PTP DI fusion protein it is possible to determine the amount of PTP DI produced by the RD cell line. EXAMPLE 7 Identification of a Molecule That Stimulates or Inhibits Enzymatic Activity of a PTP-D Protein or Glycoprotein The cDNA containing the entire coding region of PTP DI or a functional portion thereof is inseπed into the mammalian expression vector pcDNA I (Cat.. No. V490-20, Invitrogen, San Diego) using standard techniques (Ausubel et al, Current Protocols in Molecular Biology, John Wiley & Sons, New York (1988)). The 293 cell transient expression system described by Gorman et al, Virology 777:377-385 (1989) is used for production of enzymatically active PTP DI. Using standard techniques, the 293 cells are cultured in 5% CO, at 37°C in Dulbecco's Modified Eagle Medium (Cat. No. a041-02430, Gibco, Life Technologies Ltd., Paisley, Scotland) supplemented with 10 percent (v/v) fetal calf serum (Gibco). Ten μg of the plasmid construct PTP-D 1/pcDNA I are mixed with 0.5 ml 0.25 M CaCl 2 and 0.5 ml 2xBBS (50 mM N,N-bis(2-hydroxyethyl)-2- aminoethane-sulfonic acid (BES), 280 mM NaCl, 1.5 mM Na 2 HPO 4 ) and used for transfection of 1.5 x 10 6 203 cells in a 10 cm Petri dish as described by Chen & Okayama (Mol Cell Biol. 7:2745-2752 (1987)). The cells are incubated 24 hours at 37°C under 3 % CO 2 after the addition of the Ca- phosphate-DNA precipitate, then washed once in DMEM supplemented with 10 percent fetal calf serum and incubated in fresh medium for additional 24 hours at 37°C under 5 % CO 2 . The medium is removed and the cells lysed in 1.0 ml of lysis buffer (20 mM HEPES pH 7.5, 150 mM NaCl, 10 percent glycerol, 1.0 percent Triton XlOO, 1.5 mM MgCU, 4 mM Ethylene Glycol- bis(/3-aminoethyIethyl ether) N,N,N',N'-tetraacetate (EGTA; Sigma ED2SS), 10 μglv~\ aprotinin, 1 mM PMSF). The cell lysates are centrifuged at 2500xg for 2 minutes at 4°C. The supernatant is removed and 100 μ\ aliquots are quick-frozen in liquid nitrogen and stored at -70° C until use. Three different substrates are used for the evaluation of potential inhibitors or stimulators of PTP-D 1 phosphatase activity: 1) p-nitrophenyl phosphate (pNP-P; Sigma 104-0); 2) 32 P-labeled Raytide (Oncogene Science Inc., Manhasset, NY); 3) 32 P-labeIed bovine myelin basic protein (MBP). Substances which either decrease or increase die activity of PTP-Dl against one or more of these substrates are analyzed further. The activity of PTP-Dl towards pNP-P is measured essentially as described by N.K. Tonks et al, J. Biol Chem. 263:6131-6131 (1988)). Using microtiter plates, ten μl of the 293 lysate from above are incubated with 100 μl of pNP-P (30 and 100 mM, respectively) at room temperature. The absorbance is read with one minute intervals in Dynatech MR5000 reader. The substances to be analyzed for stimulatory or inhibitory activities are added to the PTP-D1/293 cell lysate 5 minutes prior to the addition of pNP-P. Labeling of Raytide and mveln basic protein with 32 P The activity of PTP-Dl towards 32 P-labeled Raytide™ is measured essentially as described by Krueger et al. (EMBO J. P:3241-3252 (1990)). The syndietic peptide Raytide is labeled with 32 P using the tyrosine kinase p60 c"arc according to the manufacturer's instructions (Oncogene Science) with minor modifications. In brief, 2 μl of poo* 5"3 " are mixed with 20 μl Raytide (1 mg/ml) and 108 μl of kinase buffer (50 mM HEPES pH 7.5 containing 10 mM MgCl 2 , 0.2% (v/v) /3-mercaptoethanol, 30 μM ATP and 50 μCi [γ- 22 P]ATP). The mixture is incubated at 37°C for 16 hours, and the reaction is stopped by addition of 500 μl of 20 percent (w/v) trichloroacetic acid (TCA) in 20 mM NaH 2 P0 4 and 100 μl of 5 mg/ml of acetylated bovine serum albumin. The mixture is centrifuged, die precipitate is washed three times in 20 percent TCA/20 mM NaH 2 PO 4 , and finally redissolved in 0.2 M Tris-Cl pH 8.0. Myelin basic protein (Sigma) is labeled with a procedure similar to that used for labeling of Raytide as described by Guan et al, Nature 350:359-362 (1991). Thirty μg of MBP is labeled in a 60 μl reaction containing the following components: 50 mM HEPES buffer pH 7.5,- 10 mM MgCl 2 , 0.067% 3-mercaptoethanol, 0.05 mM ATP including 150 Ci [γ- 32 P]ATP and 4U p43 v~ — kinase (Oncogene Science). The mixture is incubated for 60 minutes at 30°C, and the reaction is stopped by addition of ice-cold trichloroacetic acid to a final concentration of 20 percent. After 30 minutes on ice, the precipitate is washed three times in 20 percent TCA and redissolved in 100 μl H 2 O. The PTPase activity assay using Ravtide or MBP Five μl lOx PTPase buffer (25 mM HEPES pH 7.3, 5 mM EDTA, 10 mM ditbiσthreitol) are ixed with a) 5 μl 32 P-Jabeled Raytide or MBP (corresponding to 10-20 x 10 4 counts per minutes), b) 5, 10 and 25 μl, respectively, of the PTP-D 1/293 cell lysate, and c) H 2 O to a final volume of 50 μl. The reaction is stopped after incubation for 30 minutes at 37°C. In the case of Raytide, the reaction is stopped by addition of 0.75 ml acidic charcoal mixture (Krueger et αl, EMBO J. 9:3241-3252 (1990)): 0.9 M HCl, 90 mM sodium pyrophosphate, 2 mM NaH 2 P0 4 , 4% (v/v) Norit A (Sigma)). After mixing and cenrrffugation, 400 μl of the supernatant are removed and the amount of radioactivity measured. When using MBP as a substrate, the reaction is stopped by 20 percent TCA (final volume). The amount of 3 P in the supernatant is then measured. The substances to be analyzed for stimulatory or inhibitory activities are added to the PTP-D 1/293 ceil lysate 5 minutes prior to initiation of the assays. SEQUENCΞ LISTING (1) GENERAL INFORMATION: (i) APPLICANT: Ullrich, Axel Moller, Niels P.H. Moller, Karin B. (ii) TITLE OF INVENTION: PTP-D SUBFAMILY OF PROTEIN TYROSINE PHOSPHATASES (iii) NUMBER OF SEQUENCES- 38 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: Sterne, Kessler, Goldstein 4 Fox (B) STREET: I22S Connecticut Avenue, M.W. (C) CITY: Washingtion (D) STATE: D.C (E) COUNTRY: U.S.A. (F) ZIP: 2003S (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floopy disk (B) COMPUTER: IBM PC * comestible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patent n Release fel.O, Version #1.25 (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: To be assigned ~ (3) FILING DATE: herewith (C) CLASSIFICATION: (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Shaffer, Robin E. (B) REGISTRATION NUMBER: 34,249 (C) REFERENCS/DOCXΞT NUMBER: 1406.01S0000 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: (202) 833-7S33 (B) TELEFAX: (202) 833-871S (2) INFORMATION FOR SEQ ID NO:l: (i) SEQUENCE CHARACTΞS-ISTI S: (A) LENGTH: 6 amino acids (B) TYPE: amino acid " £D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: PβDtide (B) LOCATION: 6 (D) OTHER INFORMATION: /note= "This amino acid ' ay be substitu ed with Asparagine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l: Aso Tyr lie Asn Ala Ser 1 " 5 (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: S amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: Cvs Xaa Xaa Tyr Trp Pro 1 * 5 (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (D) TOPOLOGY: iroth (ii) MOLECULE TYPE: Deocide (ix) FEATURE: (A) NAME/KEY: PeDCide (3) LOCATION: 1 (D) OTHER INFORMATION: /note= "This amino acid may be substituted with Valine." (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3 lie Val Met Xaa Xaa Xaa Xaa Glu 1 5 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: S amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: pepcide (ix) FEATURE: (A) NAME/KEY: Pepcide (B) LOCATION: 1 (D) OTHER INFORMATION: /note= "This amino acid may be substituced with Asparagine." iiX; FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 6 (D) OTHER INFORMATION: /note= "This amino acid may be substituted with Asparagine." (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: Asp Tyr lie Asn Ala Ser 1 5 (2) INFORMATION FOR SEQ ID NO:S: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: S amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (ix) FEATURE ' : (A) NAME/KEY: Peptide (3) LOCATION: δ (D) OTHER INFORMATION: /notes "This amino acid may be substituted with Asparagine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:S: Gly Tyr lie Asn Ala Ser 1 5 2) INFORMATION FOR SEQ ID NO:δ : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: pepcide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: Ser Xaa Xaa Tyr Tr-o Pro 1 S (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 aniaα -acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: lie Ala Met Val Xaa Xaa Xaa Xaa Glu 1 5 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: -amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: Peotide (B) LOCATION: 6 (D) OTHER INFORMATION: /note= "This amino acid may be substituted wich Asparagine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8 : Asn Tyr lie Asn Ala Ser 1 S (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: Peptide (B) LOCATION: 1 (D) OTHER INFORMATION: /note= "This amino acid may be substituted with either Valine or Leucine." (ix) FEATURE: (A) NAME/KEY: PβDtide (B) LOCATION: 3 (D) OTHER INFORMATION: /noce= "This amino acid may be substituted -firh eicπer Isoleucine or Leucine." (ix) FEATURE: (A) NAME/KEY: PβDtide (B) LOCATION: 4 (D) OTHER INFORMATION: /note- "This amino acid may be either Leucine, Isoleucine or Methionine." (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: lie Val Met Val Xaa Xaa Xaa Xaa Glu 1 5 (2) INFORMATION FOR SEQ ID SO :10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: ACTTTCTTGG ACGAGAGATG AGTTCGATGG 30 (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 bast: pairs (B TΪPΣ- nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: CCTCGAACTA GTCCATCGCA GCTGACAGTG 30 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12 Phe Tro Xaa Met Xaa Trp 1 " S (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCL CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: Dβotide (ix) FEATURE: (A) NAME/KEY: Peotide (B) LOCATION: 6 (D) OTHER INFORMATION: /note= "This amino acid may be substituted with either Isoleucine or Valine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13 His Cys Ser Ala Gly Ser Gly 1 5 (2) INFORMATION FOR SEQ ID NO:14; (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: ATAGCAATGG TGACAGCAGA A 21 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:IS: Cys Tyr Ala Thr Thr Gly 1 5 (2) INFORMATION FOR SEQ ID NO:lδ: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: DNA (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: AGTCGACCTC GAGTTCGAGT TCGAGCAGTA AGCA 34 (2) ' NFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: S amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: Gin Glu Arσ Thr Val Trp 1 S (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: GGTTCGAACT CGAGTTCGAC TGTCT.CTCT 29 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19 ATAGCAATGG TGACAGCAGA A 21 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: misc_ eature (B) LOCATION: 6 (D) OTHER INFORMATION: /noce= "This nucleotide may be substituted with Guanine" (ix) FEATURE: (A) NAME/KEY: misc_feature (B) LOCATION: 8 (D) OTHER INFORMATION: /noce= "This nucleotide may be substituted with Thymine. " (ix) FEATURE: "This nucleotide may be su st tute w t Cycosine, Guanine or Adenine." (ix) FEATURE: (A) NAME/KEY: misc_feature (B) LOCATION: 12 (D) OTHER INFORMATION: /noce= "This nucleotide may be substituted with Cycosine, Guanine or Adenine." (ix) FEATURE: (A) NAME/KEY: misc_feature (B) LOCATION: 15 (D) OTHER INFORMATION: /noce= "This nucleocide may be substituted with Cycosine, Guanine or Adenine." (ix) FEATURE: (A) NAME/KEY: misc_feacure (B) LOCATION: 18 (D) OTHER INFORMATION: /noce= "This nucleotide may be substituted with Adenine." (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: CGCCCAACTC CTGCTCTGCA GTG „ 23 (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 40 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: GATCTCCGAA TTCCATGGAT CCAGGCCTCT AGAAGCTTAC 40 (2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 40 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE; DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: AATTGTAAGC TTCTAGAGGC CTGGATCCAT GGAATTCGGA 40 (2) INFORMATION FOR SEQ ID NO:23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: .261 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION; SZQ ID NO: 3: TTTTGGCAGA TGGTATGGGA ACAGGGAATT GCAATTATAG CAATGGTGAC AGCAGAAGAG 60 GAGGGTNGAN NGGAGAAGAG CTTTAGGTAC TGGCCACGAC TTGGTTCCAG GCACAACACT 120 GTCACCTATG GAAGGTTTAA GATCACGACC CGGTTCCGCA CAGACTCTGG CTGCTATGCC 180 ACCACAGGCC TGAAGATGAA GCACCTCCTT ACCGGGCAAG AGAGGACCGT CTGGCNNCTC 240 CAATACACAG ACTGGCCTGA A 2δl (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 87 amino acids (B) TYPE: amino acid (D) TOPOLOGY: boch (ii) MOLECULE TYPE: pepcide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: Phe Tr? Gin Met Val Trp Glu Gin Gly He Ala He He Ala Met Val 1 5 10 IS .Thr Ala Glu Glu Glu Gly Xaa Xaa Glu Lys Ser Phe Arg Tyr TΓD Pro 20 2S . 30 Arg Leu Gly Ser Arg His Asn Thr Val Thr Tyr Gly Arg Phe Lvs He 35 40 45 Thr Thr Arg Phe Arg Thr Asp Ser Gly Cys Tyr Ala Thr Thr Gly Leu 50 55 60 Lys Met Lys His Leu Leu Thr Glv Gin Glu Arg Thr Val Trp Xaa Leu 65 70 * 75 80 Gin Tyr Thr Asp Trp Pro- Glu 85 (2) INFORMATION FOR SEQ ID NO:25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 270 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID N0;2≤; TTCTGGCGGA TGATCTGGGA GCAGGGAGTG AATGTGATTG CCATGGTCAC TGCAGAGGAG 60 GAGGGTGGAC GAACCAAAAG CCACCGATAC TGGCCCAAAC TAGGTTCAAA GCACAGCTCA 120 GCCACCTATG GCAAGTTCAA GGTCACCACG AAGTTTCGAA CGGATTCTGT TTGCTATGCA 180 ACCACGGGCT TGAAGGTCAA GCACCTTTTG TCTGGGNAAG AAAGGACGGT GTGGCATTTA 240 CAATATACTG ACTGGCCTGA CTTCGGCGCC 270 (2) INFORMATION FOR SEQ ID NO:26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 90 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO-.26: Phe Trp Arg Met He Trp Glu Gin Gly Val Asn Val He Ala Met Val I S 10 15 Thr Ala Glu Glu Glu Gly Gly Arg Thr Lys Ser His Arg Tyr Tro Pro 20 25 30 Lys Leu Gly Ser Lys His Ser S&r Ala Thr Tyr Gly Lys Phe Lys Val 35 40 45 Thr Thr Lys Phe Arg Thr ASD Ser Val Cys Tyr Ala Thr Thr Gly Leu 50 55 * 60 . Lys Val Lvs His Leu Leu Ser Gly Xaa Glu Arg Thr Val Trs His Leu 65 * 70 75 80 Gin Tyr Thr Asp Trp Pro Asp Phe Gly-Ala 85 90 (2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 60 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: Met Val Trp Glu Gin Lys Ser Arg Gly Val Val Met Leu Asn Arg Val I S 10 IS Met Glu Lys Gly Ser Leu Lys Cys Ala Gin Tyr Trp Pro Gin Lys Glu 20 25 30 Glu Lys Glu Met He Phe Glu Asp Thr Asn Leu Lys Leu Thr Leu He 35 40 * 45 Ser Glu Aso He Lys Ser Tyr Tyr Thr Val Arg Gin SO * 55 60 (2) INFORMATION FOR SEQ ID NO:28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 60 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: Met Val Trp Glu Gin Gly He Ala He He Ala Met Val Thr Ala Glu 1 5 10 IS Glu Glu Gly Xaa Xaa Glu Lys Ser Phe Arg Tyr Tro Pro Arg Leu Gly 20 25 30 Thr Arg His Asn Thr Val Thr Tyr Gly Arg Phe Lys He Thr Thr Arg 3S 40 45 Phe Arg Thr ASD Ser Gly Cys Tyr Ala Thr Thr Gly 50 " 55 60 (2) INFORMATION FOR SEQ ID NO:29: <i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 60 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: Met He Trp Glu Gin Gly Val Asn Val He Ala Met Val Thr Ala Glu 1 5 . 10 15 Glu Glu Gly Gly Arg He Lys Ser His Arg Tyr Trp Pro Lys Leu Glv 20 25 30 Ser Lys His Ser Ser Ala Thr Tyr Gly Lys Phe Lys Val Thr Thr Lys 35 40 45 Phe Arg Thr Asp Ser Val Cys Tyr Ala Thr Thr Gly 50 55 60 (2) INFORMATION FOR SEQ ID NO:30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 60 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: pepcide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: Leu Glu Leu Glu Asn Leu Thr Thr Gin Glu Thr Arg Glu He Leu His 1 5 10 15 Phe His Tyr Thr Thr Trp Pro ASD Phe Gly Val Pro Glu Ser Pro Ala 20 25 30 Ser Phe Leu Asn Phe Leu Phe Lys Val Arc Glu Ser Gly Ser Leu Ser 35 40 " 45 Pro Glu His Gly Pro Val Val Val His Cvs Ser Ala SO 55 " 60 (2) INFORMATION FOR SEQ ID NO:31: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 amino acids (B) TYPE: amino acid (D) TOPOLOGY: boch (ii) MOLECULE TYPE: pepcide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:31: Leu Lys Met Lys His Leu Leu Thr Gly Gin Glu Arσ Thr Val Tn. Xaa 1 5 10 IS " Leu Gin Tyr Thr ASD Trp Pro Glu His Gly Cys Pro Glu 20 " 2S (2) INFORMATION FOR SEQ ID NO:32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE; peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2: Leu Lys Val Lys His Leu Leu Ser Gly Xaa Glu Arg Thr Val Trp His 1 5 10 15 " Leu Gin Tyr Thr ASD TTΌ Pro ASD Phe Gly Ala 20 " 25 (2) INFORMATION FOR SEQ ID NO: 3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 300 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: boch (D) TOPOLOGY: boch (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: GATTTTTGGC AGATGGTATG GGAACAGGGA ATTGCAATTA TAGCAATGGT GACAGCAGAA SO GAGGAGGGTN GANNGGAGAA GAGCTTTAGG TACTGGCCAC GACTTGGTTC CAGGCACAAC 120 ACTGTCACCT ATGGAAGGTT TAAGATCACG ACCCGGTTCC GCACAGACTC TGGCTGCTAT 180 GCCACCACAG GCCTGAAGAT GAAGCACCTC CTTACCGGGC AAGAGAGGAC CGTCTGGCNN 240 CTCCAATACA CAGACTGGCC TGAACATGGC TGTCCAGAAG ACCTCAAGGG AiTTTTATCA 300 (2) INFORMATION FOR SEQ ID NO:34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 270 base pairs (3) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: boch (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: TTCTGGCGGA TGATCTGGGA GCAGGGAGTG AATGTGATTG CCATGGTCAC TGCAGAGGAG SO GAGGGTGGAC GAACCAAAAG CCACCGATAC TGGCCCAAAC TAGGTTCAAA GCACAGCTCA 120 GCCACCTATG GCAAGTTCAA GGTCACCACG AAGTTTCGAA CGGATTCTGT TTGCTATGCA 180 ACCACGGGCT TGAAGGTCAA GCACCTTTTG TCTGGGNAAG AAAGGACGGT GTGGCATTTA 240 CAATATACTG ACTGGCCTGA CTTCGGCGCC 270 (2) INFORMATION FOR SEQ ID NO:35: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 150 -amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: pepcide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35 : Glu Trp Asp Tyr lie Ala Thr Gin Gly Pro Leu Gin Asn Thr Cvs Gin I S 10 IS Asp Phe Trp Gin Met Val Trp Glu Gin Gly lie Ala He He Ala Met 20 25 30 Val Thr Ala Glu Glu Glu Gly Xaa Xaa Glu Lys Ser Phe Arg Tyr Trp 35 * 40 4S Pro Arg Leu Gly Ser Arg His Asn Thr Tyr Thr Tyr Gly Arg Phe Lys SO 55 60 He Thr Thr Arg Phe Arg Thr ASD Ser Gly Cys Tyr Ala Thr Thr Gly 65 70 75 80 Leu Lys Met Lys His Leu Leu Thr Gly Gin Glu Arg Thr Val Trp Xaa 35 90 95 Leu Gin Tyr Thr Asp Trp Pro Glu His Gly Cys Pro Glu Asp Leu Lys 100 * • 10S 110 Gly Phe Leu Ser Tyr Leu Glu Glu He Gin Ser Val Arg Arg His Thr IIS _ 120 125 Asn Ser Thr Ser ASD Pro Gin Ser Pro Asn Pro Pro Leu Leu Val Xaa 130 135 140 Cys Ser Ala Gly Val Gly 145 ISO (2) INFORMATION FOR SEQ ID NO:36: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 90 amino acids (B) TYPE: amino acid (D) TOPOLOGY: both (ii) MOLECULE TYPE: Deotide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: Phe Trp Arg Met He Trp Glu Gin Gly Val Asn Val He Ala Met Val 1 5 10 IS Thr Ala Glu Glu Glu Gly Gly Arg T x Lys Ser His Arg Tyr TΓD Pro 20 25 30 Lys Leu Gly Ser Lys His Ser Ser Ala Thr Tyr Gly Lys Phe Lys Val 35 40 45 Thr Thr Lys Phe Arg Thr Asp Ser Val Cys Tyr Ala Thr Thr Gly Leu 50 55 60 Lys Val Lys His Leu Leu Ser Gly Xaa Glu Arg Thr Val Trp His Leu 65 70 75 80 Gin Tyr Thr ASD Trp Pro Asp Phe Gly Ala 85 90 (2) INFORMATION FOR SEQ ID NO:37: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 877 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: boch (D) TOPOLOGY: boch (ii) MOLECULE TYPE: DNA -70- (xi ) SEQUENCE DESCRI PTION : SEQ ID NO : 37 : GAATTCTTAA GAAACGGCTA GTTGATGGGG AGTGCTCAAC AGCACGACTC CCTGAAAATG SO CAGAAAGAAA TCGATTCCAA GATGTTCTTC CTTATGATGA TGCGAGAGTG GAGTTGGTCC 120 CAACTAAAGA AAACAACACT GGTTACATCA ACGCATCACA TATTAAGGTC TCTGTCAGTG 180 GAATCGAATG GGATTATATT GCCACACAGG GACCATTACA GAATACCTGT CAAGATTTTT 240 GGCAGATGGT ATGGGAACAG GGAATTGCAA TTATAGCAAT GGTGACAGCA GAAGAGGAGG 300 GTNGANNGGA GAAGAGCTTT AGGTACTGGC CACGACTTGG TTCCAGGCAC AACACTGTCA 360 CCTATGGAAG GTTTAAGATC ACGACCCGGT TCCGCACAGA CTCTGGCTGC TATGCCACCA 420 CAGGCCTGAA GATGAAGCAC CTCCTTACCG GGCAAGAGAG GACCGTCTGG CNNCTCCAAT 480 ACACAGACTG GCCTGAACAT GGCTGTCCAG AAGACCTCAA GGGATTTTTA TCATATCTTG 540 AAGAGATCCA GTCTGTTCGA CGCCATACAA ATAGCACAAG TGATCCCCAA AGCCCCAACC 600 CTCCGTTGTT GGTCCACTGC AGTGCTGGGG TAGGAAGGAC TGGCGTGGTG ATTTTGTCGG 660 AGATCATGAT CGCCTGCCTG GAACACAATG AGGTGCTGGA CATCCCGAGA GTGCTGGACA 720 TGCTGAGGCA ACAGAGAATG ATGCTGGTGC AGACTCTCTG CCAGTACACA TTTGTGTACA 780 GAGTCCTCAT CCAGTTCCTG AAAAGCTCCA GGCTCATCTA AGCTCCCACA ATTTCTTACG 840 GGGCCAGTCA TGTGAAGCGT TTACAGCTTA AAAAAAAA 878 (2 ) INFORMATION FOR SEQ ID NO : 38 : ( i ) SEQUENCE CHARACTERISTI CS : (A) LENGTH : 272 amino acids (B) TYPE : amino acid (D) TOPOLOGY : boch ( ii ) MOLECULE TYPE : pepcide (xi ) SEQUENCE DESCRIPTION : SEQ ID NO : 38 : He Leu Lys Lys Arg Leu Val Asp Gly Glu Cys Ser Thr Ala Arg Leu 1 5 10 IS Pro Glu Asn Ala Glu Arg Asn Arg Phe Gin Asp Val Leu Pro Tyr ASD 20 25 30 Asp Ala Arg Val Glu Leu Val Pro Thr Lys Glu Asn Asn Thr Gly Tyr 35 40 45 He Asn Ala Ser His lie Lys Val Ser Val Ser Gly He Glu Trs ASD 50 55 60 Tyr He Ala Thr Gin Gly Pro Leu Gin Asn Thr Cys Gin ASD Phe Tro 65 70 75 * 80 * Gin Met Val Trp Glu Gin Gly He Ala He He Ala Met Val Thr Ala 85 90 95 Glu Glu Glu Gly Xaa Xaa Glu Lys Ser Phe Arg Tyr Tro Pro Arσ Leu 100 105 * 110 Gly Ser Arg His Asn Thr Val Thr Tyr Gly Arg Phe Lys He Thr Thr 115 120 125 Arg Phe Arg Thr Asp Ser Gly Cys Tyr Ala Thr Thr Gly Leu Lys Met 130 135 140 Lys His Leu Leu Thr Gly Gin Glu Arg Thr Val Trp Xaa Leu Gin Tyr 145 150 155 160 Thr ASD Trp Pro Glu His Gly Cys Pro Glu ASD Leu Lys Gly Phe Leu 165 170 " 175 Ser Tyr Leu Glu Glu He Gin Ser Val Arg Arg His Thr Asn Ser Thr 180 185 190 Ser ASD Pro Gin Ser Pro Asn Pro Pro Leu Leu Val His Cys Ser Ala 195 200 205 Gly Val Gly Arg Thr Gly Val Val He Leu Ser Glu He Mec He Ala 210 215 220 Cys Leu Glu His Asn Glu Val Leu ASD He Pro Arg Val Leu ASD Met 225 230 23 r i " 240 Leu Arg Gin Gin Arg Mec Met Leu Val Gin Thr Leu Cys Gin Tyr Thr 245 250 255 Phe Val Tyr Arg Val Leu He Gin Phe Leu Lvs Ser Ser Arg Leu He 260 265 " 270

Claims: What is claimed is: 1. A PTP-D protein or glycoprotein, wherein when said PTP-D protein or glycoprotein is one which occurs in nature, said PTP-D protein or glycoprotein is substantially free of other proteins or glycoproteins with which it is natively associated. 2. The PTP-D protein or glycoprotein according to claim 1 comprising a catalytic phosphatase domain comprising one, two, or three amino acid sequences selected from 1. G Y I N A S/N [SEQ. ID NO. 5], 2. S X X Y W P [SEQ. ID NO. 6], and 3. I A M V X X X X E [SEQ. ID NO. 7]. 3. The PTP-D protein or glycoprotein according to claim 1 , which does not occur in nature. 4. The PTP-D protein or glycoprotein according to claim 3, which has deleted amino acids. 5. The PTP-D protein or glycoprotein according to claim 3 , which has additional amino acids. 6. The PTP protein or glycoprotein according to claim 3, which has substituted amino cids. 7. The PTP-D protein or glycoprotein according to claim 1 , which occurs in nature and is substantially free of other proteins or glycoproteins with which it is natively associated. 8. The PTP-D protein or glycoprotein according to claim 1 comprising an amino acid sequence that has 70% or more homology with the amino acid sequence shown in Figure 1 of PTP-Dl. 9. The PTP-D protein or glycoprotein according to claim 8, which is PTD-D1. 10. The PTP-D protein or glycoprotein according to claim 1, comprising an amino acid sequence that has 70% or more identity with the amino acid sequence shown in Figure 2 of PTP-D2. 11. The PTP-D protein or glycoprotein according to claim 10, which is PTD-D2. 12. A recombinant nucleic acid construct comprising a nucleotide sequence encoding a PTP-D protein or glycoprotein. 13. The recombinant nucleic acid construct according to claim 12, which is a cDNA sequence. 14. The recombinant nucleic acid construct according to claim 12, which is a genomic DNA sequence. 15. The recombinant nucleic acid construct according to claim 12 having the nucleotide sequence of SEQ. ID: No. 23 (Figure 1). 16. The recombinant nucleic acid construct according to claim 12 having the nucleotide sequence of SEQ. ID: No. 25 (Figure 2). 17. The recombinant nucleic acid construct according to claim 12, which is an expression vehicle. 18. The recombinant nucleic acid construct of claim 17, which is a vector. 19. The recombinant nucleic acid construct of claim 17, which is a plasmid. 20. An isolated and purified nucleic acid construct comprising a nucleotide sequence encoding a PTP-D protein or glycoprotein. 21. The isolated and purified nucleic acid construct according to claim 20, having the nucleotide sequence of SEQ. ID: No. 23 (Figure 1). 22. The isolated and purified nucleic acid construct according to claim 20, having the nucleotide sequence of SEQ. ID: No. 25 (Figure 2). 23. A procaryotic host cell transformed with the nucleic acid construct of claim 17. 24. The prokaryotic host cell according to claim 23, which is a bacterium. 25. A eukaryotic host cell transformed with the nucleic acid construct of claim 17. 26. The eukaryotic host cell according to claim 25, which is a yeast cell or a mammalian cell. 27. A method for preparing a PTP-D protein or glycoprotein, comprising: (a) culturing a host cell capable of expressing said PTP-D protein or glycoprotein under culturing conditions; (b) expressing said PTP-D protein or glycoprotein; and (c) recovering said PTP-D protein or glycoprotein from said culture. 28. The method according to claim 27 wherein said host cell is a prokaryote. 29. The eL od according to claim 27 wherein said host cell is a eukaryote. 30. An antibody specific for a PTP-D molecule. 31. The antibody according to claim 30 which is monoclonal. 32. The antibody according to claim 30 which is polyclonal. 33. A method for detecting the presence of or measuring the quantity of a PTP-D protein or glycoprotein in a cell, said method comprising: (a) contacting said cell or an extract thereof with an antibody specific for an epitope of a PTP-D protein or glycoprotein; and (b) detecting the binding of said antibody to said cell or extract thereof, or measuring the quantity of antibody bound, thereby determining the presence of or measuring the quantity of said PTP-D protein or glycoprotein. 34. A method for detecting the presence of a nucleic acid sequence encoding a PTP-D protein, or a nucleic acid construct encoding a mutant PTP- D protein or glycoprotein, in a cell or a subject, comprising: (a) contacting a cell or an extract thereof from said subject with an oligonucleotide probe encoding at least a portion of said PTP-D protein or glycoprotein or at least a portion of said mutant PTP- D protein or glycoprotein under hybridizing conditions; and (b) measuring the hybridization of said probe to nucleic acid of said cell, thereby detecting the presence of said nucleic acid construct. 35. The method of claim 34, additionally comprising before step (a): (c) selectively amplifying the amount of said nucleic acid of said cell encoding said PTP-D protein or glycoprotein. 36. A method for identifying in a chemical or biological preparation a compound capable of binding to a PTP-D protein or glycoprotein, said method comprising: (a) attaching said PTP-D protein or glycoprotein, or the compound- binding portion thereof to a solid phase matrix; (b) contacting said chemical or biological preparation with said solid phase matrix allowing said compound to bind, and washing away any unbound material; and (c) detecting the presence of said compound bound to said solid phase. 37. A method' for isolating from a complex mixture a compound capable of binding to a PTP-D protein or glycoprotein, said method comprising: (a) attaching said PTP-D protein or glycoprotein, or a compound- binding portion thereof, to a solid phase matrix; (b) contacting said complex mixture with said solid phase matrix allowing said compound to bind, and washing away any unbound material; and (c) eluting said bound compound, thereby isolating said compound. 38. A method for identifying a molecule capable of stimulating or inhibiting the enzymatic activity of a PTP-D protein or glycoprotein, said method comprising: (a) contacting said compound with said PTP-D protein or glycoprotein in pure form, in a membrane preparation, or in a whole live or fixed cell; (b) incubating said mixture of step (a) for a sufficient interval; (c) measuring the enzymatic activity of said PTP-D protein or glycoprotein; (d) comparing said enzymatic activity to that of said PTP-D protein or glycoprotein incubated without said compound, thereby determining whether said PTP-D protein or glycoprotein stimulates or inhibits said activity. 39. The method according to claim 38, wherein said PTP-D protein or glycoprotein in step (a) is a fragment of a PTP-D protein or glycoprotein. 40. A pharmaceutical composition for treating or preventing a disease with abnormal PTP-D protein or glycoprotein, said composition comprising a PTP-D protein or glycoprotein and a pharmaceutically acceptable carrier. 41. A pharmaceutical composition for treating or preventing a disease with abnormal PTP-D protein or glycoprotein, said composition comprising a molecule in an amount effective to stimulate or inhibit enzymatic activity of a PTP-D protein or glycoprotein. 42. A method for treating or preventing a disease with abnormal PTP-D protein or glycoprotein in a subject, comprising administering to said subject said composition according to claim 40. 43. A method for treating or preventing a disease with abnormal PTP-D protein or glycoprotein in a subject, comprising administering to said subject said composition according to claim 41. 44. A pharmaceutical composition comprising a PTP-D protein or glycoprotein and a pharmaceutically acceptable carrier. 45. A pharmaceutical composition comprising a molecule in an amount effective to stimulate or inhibit enzymatic activity of a PTP-D protein or glycoprotein. 46. A method for treating or preventing a disease in a subject, comprising administering to said subject said composition according to claim 44. 47. A method for treating or preventing a disease in a subject, comprising administering to said subject said composition according to claim 45.

Inventors: BACH-MOLLER KARIN, MOLLER NILS PETER HUNDAHL, ULLRICH AXEL, BACH-MOELLER, KARIN, MOELLER, NILS, PETER, HUNDAHL, ULLRICH, AXEL
Applicants: MAX PLANCK GESELLSCHAFT, MAX-PLANCK-GESELLSCHAFT ZUR FOERDERUNG DER WISSENSC
Application year: 1993
Main classification: C12N15
IPC codes: A61K38, A61K39, A61P35, C07H21, C12N1, C12N5, C12N9, C12N15, C12P21, C12Q1, C12R1, G01N33