bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue‐specific expression of multiple mRNA variants of the mouse estrogen receptor α gene
Authors: Kos Martin , O'Brien Sinead , Flouriot Gilles , Gannon Frank
Published: July 2002

The isolation of five new mouse estrogen receptor α mRNA variants (mERα A, B, F1, F2 and H) is described. All of these transcripts are generated by alternative splicing and all encode the 66 kDa ERα protein that the previously identified mRNA C variant generates. However, these transcripts differ in their 5′ untranslated regions. RT‐PCR and S1 nuclease protection assays revealed a tissue‐ and sex‐specific expression pattern of all variants. The C and F mRNA variants are the predominantly expressed mERα variants in mouse. The expression of mERα H mRNA is restricted to liver, although female mice produce around a five fold higher level of this transcript than males. Our results show that the mERα gene is a complex genomic unit in mice that exhibits alternative splicing which is regulated in a tissue‐specific manner.
SGD1 encodes an essential nuclear protein of Saccharomyces cerevisiae that affects expression of the GPD1 gene for glycerol 3‐phosphate dehydrogenase
Authors: Akhtar Noreen , Påhlman Anna-Karin , Larsson Katrin , Corbett Anita H. , Adler Lennart
Published: July 2002

We here report the identification of the previously uncharacterized SGD1 gene, encoding a 102.8‐kDa protein containing a leucine zipper region and a bipartite nuclear localization signal. Deletion of SGD1 results in loss of cell viability, while an increased dosage of SGD1 partially suppresses the osmosensitivity of pbs2Δ and hog1Δ mutants that are defective in the osmosignaling high osmolarity glycerol (HOG) mitogen‐activated protein kinase pathway. The rescued mutants display a partially re‐established transcriptional control of the osmostress‐induced expression of GPD1, a target gene of the HOG pathway encoding NAD+‐dependent glycerol 3‐phosphate dehydrogenase, and a partially recovered hyperosmolarity‐induced production of glycerol. Consistent with Sgd1p affecting the transcriptional control of GPD1, a functional green fluorescent protein tagged Sgd1p is localized to the cell nucleus.
A novel patatin‐like gene stimulated by drought stress encodes a galactolipid acyl hydrolase
Authors: Matos Ana Rita , d'Arcy-Lameta Agnès , França Marcel , Pêtres Stéphane , Edelman Léna , Kader Jean-Claude , Zuily-Fodil Yasmine , Pham-Thi Anh Thu
Published: July 2002

A cDNA (Vupat1) encoding a predicted 43 kDa protein was isolated from drought‐stressed cowpea (Vigna unguiculata) leaves. It has homology with patatin, a potato tuber storage protein with lipolytic acyl hydrolase activity. The recombinant protein VUPAT1 expressed in the baculovirus system displays preferentially galactolipid acyl hydrolase activity. Phospholipids are very slowly hydrolyzed and apparently triacylglycerols are not deacylated. Vupat1 promoter contains putative drought‐inducible sequences. Northern blots showed that gene expression is stimulated by drought stress and is more pronounced in a drought‐sensitive cultivar than in a drought‐tolerant one. An involvement in drought‐induced galactolipid degradation is proposed for VUPAT1.
Pharmacological properties of the mouse neurotensin receptor 3. Maintenance of cell surface receptor during internalization of neurotensin
Authors: Navarro Valérie , Martin Stéphane , Sarret Philippe , Nielsen Morten S. , Petersen Claus M. , Vincent Jean-Pierre , Mazella Jean
Published: July 2002

We recently reported the molecular identification of a new type of receptor for the neuropeptide neurotensin (NT), the neurotensin receptor 3 (NTR3), identical to sortilin, which binds receptor‐associated protein. Here, we demonstrate that the cloned mouse NTR3 is expressed on the plasma membrane of transfected COS‐7 cells. The mouse NTR3 is detectable by photoaffinity labeling and immunoblotting at the cell surface as a 100 kDa N‐glycosylated protein. Biochemical analysis and confocal microscopic imaging clearly indicate that NT is efficiently internalized after binding to NTR3, and that despite this internalization, the amount of receptor present on the cell surface is maintained.
A thermostable K+‐stimulated vacuolar‐type pyrophosphatase from the hyperthermophilic bacterium Thermotoga maritima
Authors: Pérez-Castiñeira José R. , López-Marqués Rosa L. , Losada Manuel , Serrano Aurelio
Published: July 2002

Current evidence suggests the occurrence of two classes of vacuolar‐type H+‐translocating inorganic pyrophosphatases (V‐PPases): K+‐insensitive proteins, identified in eukaryotes, bacteria and archaea, and K+‐stimulated V‐PPases, identified to date only in eukaryotes. Here, we describe the functional characterization of a thermostable V‐PPase from the anaerobic hyperthermophilic bacterium Thermotoga maritima by heterologous expression in Saccharomyces cerevisiae. The activity of this 71‐kDa membrane‐embedded polypeptide has a near obligate requirement for K+, like the plant V‐PPase, and its thermostability depends on the binding of Mg2+. Phylogenetic analysis of protein sequences consistently assigned the T. maritima V‐PPase to the K+‐sensitive class of V‐PPases so far only known for eukaryotes. The finding of a K+‐stimulated V‐PPase also in a member of a primitive eubacterial lineage strongly supports an ancient evolutionary origin of this group of pyrophosphate‐energized proton pumps.
Deletion of the acidic‐rich domain of the IL‐2Rβ chain increases receptor‐associated PI3K activity
Authors: Ciprés Angel , Carrasco Silvia , Mérida Isabel
Published: July 2002

Interleukin‐2 (IL‐2) regulates the proliferation and homeostasis of lymphocytes through the coordinated activation of distinct signaling pathways. Deletion of the acidic‐rich domain of the IL‐2 receptor β chain (IL‐2Rβ) prevents association of Src tyrosine kinases to the receptor, as well as IL‐2‐induced Akt activation. Cells bearing this deletion (BafβΔA) maintain full proliferation in response to IL‐2 both in vivo and in vitro, suggesting that those pathways are dispensable for this important function of IL‐2. In this study, we re‐examined phosphatidylinositol‐3 kinase (PI3K) activation in BafβΔA cells and found that, in BaF/3 IL‐2RβΔA cells, deletion of the acidic domain induced constitutive activation of the receptor‐associated PI3K activity. This, in turn, was responsible for the higher basal Akt activity observed in cells expressing this deletion. Based on these data, and since pharmacological abrogation of PI3K activity prevented IL‐2‐driven cell proliferation of BafβΔA cells, we conclude that the PI3K/Akt pathway is still functionally relevant in cells bearing this mutation. Moreover, we show that the PI3K‐induced signals are, at least in part, responsible for c‐myc expression. In conclusion, we have used this model to better identify those signals that are integral components of the molecular mechanisms responsible for IL‐2‐regulated cell proliferation.
Mice lacking histidine decarboxylase exhibit abnormal mast cells
Authors: Ohtsu Hiroshi , Tanaka Satoshi , Terui Tadashi , Hori Yoshio , Makabe-Kobayashi Yoko , Pejler Gunnar , Tchougounova Elena , Hellman Lars , Gertsenstein Marina , Hirasawa Noriyasu , Sakurai Eiko , Buzás Edit , Kovács Péter , Csaba György , Kittel Ágnes , Okada Mikiko , Hara Masahiro , Mar Lynn , Numayama-Tsuruta Keiko , Ishigaki-Suzuki Satsuki , Ohuchi Kazuo , Ichikawa Atsushi , Falus András , Watanabe Takehiko , Nagy András
Published: July 2002

Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC‐deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked histamine‐synthesizing activity from histidine. These HDC‐deficient mice are viable and fertile but exhibit a decrease in the numbers of mast cells while the remaining mast cells show an altered morphology and reduced granular content. The amounts of mast cell granular proteases were tremendously reduced. The HDC‐deficient mice provide a unique and promising model for studying the role of histamine in a broad range of normal and disease processes.
P34cdc2 kinase is associated with cortical microtubules from higher plant protoplasts
Authors: Hemsley Rachel , McCutcheon Sandra , Doonan John , Lloyd Clive
Published: July 2002

The cell cycle regulatory enzyme p34cdc2 kinase is known to be localized to the preprophase band, the spindle and the phragmoplast, but not to interphase cortical microtubules. This was investigated further by mechanically cleaving substrate‐attached protoplasts to leave plasma membrane disks bearing microtubules freed of nuclear and cytosolic signal. Antibodies to PSTAIRE and to specific C‐terminal peptides of cdc2a, were used in immunofluorescence, protein blotting and immunogold electron microscopy to demonstrate that antigen is located on the cortical microtubules of carrot, tobacco BY‐2 and Arabidopsis cells.
Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and express a novel current
Authors: Post Marc A. , Kirsch Glenn E. , Brown Arthur M.
Published: July 2002

Heteromultimer formation between Kv potassium channel subfamilies with the production of a novel current is reported for the first time. Protein‐protein interactions between Kv2.1 and electrically silent Kv6.1 α‐subunits were detected using two microelectrode voltage clamp and yeast two‐hybrid measurements. Amino terminal portions of Kv6.1 were unable to form homomultimers but interacted specifically with amino termini of Kv2.1. Xenopus oocytes co‐injected with Kv6.1 and Kv2.1 cRNAs exhibited a novel current with decreased rates of deactivation, decreased sensitivity to TEA block, and a hyperpolarizing shift of the half maximal activation potential when compared to Kv2.1. Our results indicate that Kv channel subfamilies can form heteromultimeric channels and, for the first time, suggest a possible functional role for the Kv6 subfamily.
The dependence of the association rate of surface‐attached adhesion molecules CD2 and CD48 on separation distance
Authors: Pierres Anne , Benoliel Anne Marie , Bongrand Pierre , van der Merwe P.Anton
Published: July 2002

© Federation of European Biochemical Societies.
Oscillation of ADP‐ribosyl cyclase activity during the cell cycle and function of cyclic ADP‐ribose in a unicellular organism, Euglena gracilis
Authors: Masuda Wataru , Takenaka Shigeo , Inageda Kiyoshi , Nishina Hiroshi , Takahashi Katsunobu , Katada Toshiaki , Tsuyama Shingo , Inui Hiroshi , Miyatake Kazutaka , Nakano Yoshihisa
Published: July 2002

In Euglena gracilis, the activity of ADP‐ribosyl cyclase, which produces cyclic ADP‐ribose, oscillated during the cell cycle in a synchronous culture induced by a light‐dark cycle, and a marked increase in the activity was observed in the G2 phase. Similarly, the ADP‐ribosyl cyclase activity rose extremely immediately before cell division started, when synchronous cell division was induced by adding cobalamin (which is an essential growth factor and participates in DNA synthesis in this organism) to its deficient culture. Further, cADPR in these cells showed a maximum level immediately before cell division started. A dose‐dependent Ca2+ release was observed when microsomes were incubated with cADPR. © 1997 Federation of European Biochemical Societies.
Involvement of PA/plasmin system in the processing of pro‐MMP‐9 and in the second step of pro‐MMP‐2 activation
Authors: Baramova E.N. , Bajou K. , Remacle A. , L'Hoir C. , Krell H.W. , Weidle U.H. , Noel A. , Foidart J.M.
Published: July 2002

© 1997 Federation of European Biochemical Societies.
Crystal structure of tetranectin, a trimeric plasminogen‐binding protein with an α‐helical coiled coil
Authors: Nielsen Bettina Bryde , Kastrup Jette Sandholm , Rasmussen Hanne , Holtet Thor Las , Graversen Jonas Heilskov , Etzerodt Michael , Thøgersen Hans Christian , Larsen Ingrid Kjøller
Published: July 2002

Tetranectin is a plasminogen kringle 4‐binding protein. The crystal structure has been determined at 2.8 Å resolution using molecular replacement. Human tetranectin is a homotrimer forming a triple α‐helical coiled coil. Each monomer consists of a carbohydrate recognition domain (CRD) connected to a long α‐helix. Tetranectin has been classified in a distinct group of the C‐type lectin superfamily but has structural similarity to the proteins in the group of collectins. Tetranectin has three intramolecular disulfide bridges. Two of these are conserved in the C‐type lectin superfamily, whereas the third is present only in long‐form CRDs. Tetranectin represents the first structure of a long‐form CRD with intact calcium‐binding sites. In tetranectin, the third disulfide bridge tethers the CRD to the long helix in the coiled coil. The trimerization of tetranectin as well as the fixation of the CRDs relative to the helices in the coiled coil indicate a demand for high specificity in the recognition and binding of ligands.
Identification of positively charged residues contributing to the stability of plasminogen activator inhibitor 1
Authors: Gils Ann , Lu Jie , Aertgeerts Kathleen , Knockaert Isabelle , Declerck Paul J
Published: July 2002

Plasminogen activator inhibitor 1 (PAI‐1), a member of the serpins, has a unique conformational flexibility. A typical characteristic is its intrinsic lability resulting in the conversion of the active conformation to a latent conformation. In the present study, we have evaluated the effect of substitution of positively charged residues located at the turn connecting strand s4C with strand s3C, either with negatively charged or with neutral residues, on the functional stability of PAI‐1. The following mutants were constructed, purified and characterized in comparison to wild‐type (wt) PAI‐1: PAI‐1‐R186E,R187E (Arg186→Glu and Arg187→Glu), PAI‐1‐H190E,K191E (His190→Glu and Lys191→Glu) and PAI‐1‐H190L,K191L (His190→Leu and Lys191→Leu). In contrast to wtPAI‐1 the mutants exhibited no inhibitory activity. Whereas latent wtPAI‐1 can be reactivated (up to a specific activity of 78±19%) by treatment with guanidinium chloride, a similar treatment applied to these mutants resulted in a significant but relatively small increase of specific activity (i.e. to 14%). Evaluation of the functional stability (at 37°C, pH 5.5, 1 M NaCl) revealed a strongly decreased functional stability compared to wtPAI‐1 (i.e. 3–9 h for the mutants vs. >24 h for wtPAI‐1). Further characterization by heat denaturation studies and plasmin susceptibility confirmed that removal or reversal of the positive charge on the turn connecting s4C with s3C results in PAI‐1 mutants with a highly accelerated conversion of active to latent forms. We can therefore conclude that the pronounced positive charge in the turn connecting s4C with s3C is of the highest importance for the functional stability of PAI‐1.
Enzymes as chaperones and chaperones as enzymes
Authors: Wang Chih-Chen , Tsou Chen-Lu
Published: July 2002

Chaperones and foldases are two groups of accessory proteins which assist maturation of nascent peptides into functional proteins in cells. Protein disulfide isomerase, a foldase, and ATP‐dependent proteases, responsible for degradation of misfolded proteins in cells, both have intrinsic chaperone activities. Trigger factor and DnaJ, well known Escherichia coli chaperones, show peptidyl prolyl isomerase and protein disulfide isomerase activities respectively. It is suggested that the combination of chaperone and enzyme activities in one molecule is the result of evolution to increase molecular efficiency.
The α2D/A‐adrenergic receptor‐linked membrane guanylate cyclase: a new signal transduction system in the pineal gland
Authors: Venkataraman Venkateswar , Duda Teresa , Sharma Rameshwar K.
Published: July 2002

In the pineal gland, the membrane guanylate cyclase activity was specifically stimulated by α2D/A‐adrenergic receptor (α2D/A‐AR) agonists. The agonists, however, did not stimulate the cyclase activity in the cell‐free membranes. It was possible to stimulate the cyclase in cell‐free membranes by the addition of the pineal soluble fraction, but this stimulation was Ca2+‐dependent and α2D/A‐agonist‐independent. It was also possible to achieve Ca2+‐dependent stimulation of the cyclase by the direct addition of CD‐GCAP to the isolated pineal membranes. CD‐GCAP is a Ca2+‐binding protein and is a specific activator of one of the two members of the ROS‐GC subfamily of membrane guanylate cyclases, ROS‐GC1. The soluble fraction of the pineal gland stimulated recombinant ROS‐GC1 in a Ca2+‐dependent fashion. The direct presence of both ROS‐GC1 and CD‐GCAP in the pineal was established by molecular cloning/PCR studies. The findings demonstrate the existence of a novel signal transduction mechanism – the linkage of the α2D/A‐AR signaling system with ROS‐GC1 transduction system, occurring through intracellular Ca2+ via CD‐GCAP.
Characterisation of γ‐glutamylcysteine synthethase‐heavy subunit promoter: a critical role for AP‐1
Authors: Rahman Irfan , Smith Christopher A.D , Antonicelli Frank , MacNee William
Published: July 2002

The 5′‐flanking region of human γ‐glutamylcysteine synthetase‐heavy subunit (γ‐GCS‐HS) was characterised by creating a series of chloramphenicol acetyl transferase (CAT) reporter deletion constructs. Analysis of various deleted CAT constructs revealed that a putative AP‐1 consensus sequence is required to direct the constitutive and oxidant‐mediated promoter activity. Gel mobility shift and mutation analysis of the sequence (−269 to −263 bp), showed binding of AP‐1 is involved in the oxidant‐mediated regulation of γ‐GCS‐HS promoter activity.
Topological and functional analysis of the rat liver carnitine palmitoyltransferase 1 expressed in Saccharomyces cerevisiae
Authors: Prip-Buus Carina , Cohen Isabelle , Kohl Claude , Esser Victoria , McGarry J.Denis , Girard Jean
Published: July 2002

The rat liver carnitine palmitoyltransferase 1 (L‐CPT 1) expressed in Saccharomyces cerevisiae was correctly inserted into the outer mitochondrial membrane and shared the same folded conformation as the native enzyme found in rat liver mitochondria. Comparison of the biochemical properties of the yeast‐expressed L‐CPT 1 with those of the native protein revealed the same detergent lability and similar sensitivity to malonyl‐CoA inhibition and affinity for carnitine. Normal Michaelis‐Menten kinetics towards palmitoyl‐CoA were observed when careful experimental conditions were used for the CPT assay. Thus, the expression in S. cerevisiae is a valid model to study the structure‐function relationships of L‐CPT 1.
Origins of globular structure in proteins
Authors: Doi Nobuhide , Yanagawa Hiroshi
Published: July 2002

Since natural proteins are the products of a long evolutionary process, the structural properties of present‐day proteins should depend not only on physico‐chemical constraints, but also on evolutionary constraints. Here we propose a model for protein evolution, in which membranes play a key role as a scaffold for supporting the gradual evolution from flexible polypeptides to well‐folded proteins. We suggest that the folding process of present‐day globular proteins is a relic of this putative evolutionary process. To test the hypothesis that membranes once acted as a cradle for the folding of globular proteins, extensive research on membrane proteins and the interactions of globular proteins with membranes will be required.
Refolding of Escherichia coli produced membrane protein inclusion bodies immobilised by nickel chelating chromatography
Authors: Rogl H , Kosemund K , Kühlbrandt W , Collinson I
Published: July 2002

Two distinctly different membrane proteins, which produced inclusion bodies in Escherichia coli, have been refolded to reconstitute properties appropriate to their native counterparts. The method employed utilises nickel chelating chromatography, where the solubilised inclusion bodies bind, refold and elute. Our aims were to release a large pool of membrane protein for functional, mutational and crystallisation screening studies. It is hoped that the methods described here will have a general application for other membrane proteins which have formed inclusion bodies.
An AP‐1 site in the promoter of the human IL‐5Rα gene is necessary for promoter activity in eosinophilic HL60 cells
Authors: Baltus Belinda , van Dijk Thamar B , Caldenhoven Eric , Zanders Ed , Raaijmakers Jan A.M , Lammers Jan-Willem J , Koenderman Leo , de Groot Rolf P
Published: July 2002

Interleukin‐5 (IL‐5) plays a crucial role in the proliferation, differentiation and activation of eosinophils. The IL‐5 receptor is composed of an IL‐5‐specific α subunit, which is expressed by eosinophils and basophils, and a βc‐subunit shared with the receptors for IL‐3 and GM‐CSF. We identified an AP‐1 element which is important for IL‐5Rα promoter activity in eosinophilic HL60 cells. The AP‐1 site and the previously identified EOS1 site cooperate, since single mutation of either of the sites decreased promoter activity. We show that the AP‐1 site of the IL‐5Rα promoter binds multiple proteins, including cJun, CREB, and CREM.
Residual dipolar couplings as new conformational restraints in isotopically 13C‐enriched oligosaccharides
Authors: Kiddle G.R , Homans S.W
Published: July 2002

We report the measurement of residual dipolar couplings for 13C‐enriched NeuNAcα2‐3Galβ1‐4Glc in a dilute liquid‐crystalline medium. These couplings provide long‐range conformational restraints that hitherto have not been available for oligosaccharides. We utilise these restraints in dynamical simulated annealing calculations, which support current models of the solution behaviour of the trisaccharide.
Identification and characterization of a novel splice variant of MuSK
Authors: Hesser Boris A. , Sander Andreas , Witzemann Veit
Published: July 2002

MuSK is a receptor tyrosine kinase that initiates the formation of neuromuscular junctions in response to agrin. Little is known about the ligand‐induced activation and kinase‐dependent signalling that leads to the clustering of acetylcholine receptors. The ectodomain of these molecule is composed of four Ig‐like domains. We describe here the isolation of a novel MuSK splice variant that lacks the third Ig‐like domain in its ectodomain. The corresponding RNA is the result of alternative splicing which eliminates two exons. There is 10 times less mRNA for this shorter form than for the long form of MuSK and both forms are regulated coordinately. They decrease strongly after birth and are elevated in denervated muscle. Gene transfer by muscle injection of MuSK DNA into individual muscle fibers demonstrates that kinase‐induced acetylcholine receptor clustering caused by overexpression of the two kinases does not depend on the presence of the third Ig‐like domain.
Kinetics of the interaction of endotoxin with polymyxin B and its analogs: a surface plasmon resonance analysis
Authors: Thomas Celestine J. , Surolia Avadhesha
Published: July 2002

Lipopolysaccharide, the invariant structural component of Gram‐negative bacteria, when present in minute amounts in the circulation in humans elicits ‘endotoxic shock' syndrome, which is fatal in 60% of the cases. Polymyxin B (PMB), a cyclic cationic peptide, neutralizes the endotoxin, but also induces many harmful side effects. Many peptide‐based drugs mimicking the activity of PMB have been synthesized in an attempt to reduce toxicity while still retaining the anti‐endotoxic activity. The study attempts to use the recent technique of surface plasmon resonance (SPR), in determining the kinetics of association and dissociation involved in the interaction of endotoxin with a few selected peptides that have structural features resembling PMB. The results, in conjunction with the thermodynamic data derived using isothermal titration calorimetry (ITC), stress the vital role played by amphiphilicity of the peptides and hydrophobic forces in this biologically important interaction.
Identifying and characterizing a second structural domain of protein disulfide isomerase
Authors: Darby Nigel J. , van Straaten Monique , Penka Elke , Vincentelli Renaud , Kemmink Johan
Published: July 2002

Recent protein engineering studies have confirmed the multidomain nature of protein disulfide isomerase previously suggested on the basis of analysis of its amino acid sequence. The boundaries of three domains, denoted a, a′ and b, have been determined, and each domain has been expressed as an individual soluble folded protein. In this report, the boundaries of the final structural domain, b′, are defined by a combination of restricted proteolysis and protein engineering approaches to complete our understanding of the domain organization of PDI. Using these data an optimized polypeptide construct has been prepared and characterized with a view to further structural and functional studies.
Thiamine repression and pyruvate decarboxylase autoregulation independently control the expression of the Saccharomyces cerevisiae PDC5 gene
Authors: Muller Elize H. , Richards Emma J. , Norbeck Joakim , Byrne Kerry L. , Karlsson Karl-Anders , Pretorius Gert H.J. , Meacock Peter A. , Blomberg Anders , Hohmann Stefan
Published: July 2002

The Saccharomyces cerevisiae gene PDC5 encodes the minor isoform of pyruvate decarboxylase (Pdc). In this work we show that expression of PDC5 but not that of PDC1, which encodes the major isoform, is repressed by thiamine. Hence, under thiamine limitation both PDC1 and PDC5 are expressed. PDC5 also becomes strongly expressed in a pdc1Δ mutant. Two‐dimensional gel electrophoresis of whole protein extracts shows that thiamine limitation stimulates the production of THI gene products and of Pdc5p. Deletion of PDC1 only stimulates production of Pdc5p. We conclude that the stimulation of PDC5 expression in a pdc1Δ mutant is not due to a response to thiamine limitation.
Phosphorylation of rat brain calpastatins by protein kinase C
Authors: Averna M. , De Tullio R. , Salamino F. , Melloni E. , Pontremoli S.
Published: July 2002

Calpastatin, the natural inhibitor of calpain, is present in rat brain in multiple forms, having different molecular masses, due to the presence of one (low Mr form) or four (high Mr form) repetitive inhibitory domains. Recombinant and native calpastatin forms are substrates of protein kinase C, which phosphorylates a single serine residue at their N‐terminus. Furthermore, both low and high Mr calpastatins are phosphorylated by protein kinase C at the same site. These calpastatin forms are phosphorylated also by protein kinase A, although with a lower efficiency. The incorporation of a phosphate group determines an increase in the concentration of Ca2+ required to induce the formation of the calpain‐calpastatin complex. This effect results in a large decrease of the inhibitory efficiency of calpastatins. We suggest that phosphorylation of calpastatin represents a mechanism capable to balance the actual amount of active calpastatin to the level of calpain to be activated.
NMR structure of a minimized human agouti related protein prepared by total chemical synthesis
Authors: Bolin Kimberly A. , Anderson D.Joe , Trulson Julie A. , Thompson Darren A. , Wilken Jill , Kent Stephen B.H. , Gantz Ira , Millhauser Glenn L.
Published: July 2002

The structure of the chemically synthesized C‐terminal region of the human agouti related protein (AGRP) was determined by 2D 1H NMR. Referred to as inimized gouti elated rotein, MARP is a 46 residue polypeptide containing 10 Cys residues involved in five disulfide bonds that retains the biological activity of full length AGRP. AGRP is a mammalian signaling molecule, involved in weight homeostasis, that causes adult onset obesity when overexpressed in mice. AGRP was originally identified by homology to the agouti protein, another potent signaling molecule involved in obesity disorders in mice. While AGRP's exact mechanism of action is unknown, it has been identified as a competitive antagonist of melanocortin receptors 3 and 4 (MC3r, MC4r), and MC4r in particular is implicated in the hypothalamic control of feeding behavior. Full length agouti and AGRP are only 25% homologous, however, their active C‐terminal regions are ∼40% homologous, with nine out of the 10 Cys residues spatially conserved. Until now, 3D structures have not been available for either agouti, AGRP or their C‐terminal regions. The NMR structure of MARP reported here can be characterized as three major loops, with four of the five disulfide bridges at the base of the structure. Though its fold is well defined, no canonical secondary structure is identified. While previously reported structural models of the C‐terminal region of AGRP were attempted based on Cys homology between AGRP and certain toxin proteins, we find that Cys spacing is not sufficient to correctly determine the 3D fold of the molecule.
The glucose repressor CRE1 from Sclerotinia sclerotiorum is functionally related to CREA from Aspergillus nidulans but not to the Mig proteins from Saccharomyces cerevisiae
Authors: Vautard Géraldine , Cotton Pascale , Fèvre Michel
Published: July 2002

We isolated the putative glucose repressor gene cre1 from the phytopathogenic fungus Sclerotinia sclerotiorum. cre1 encodes a 429 amino acid protein 59% similar to the carbon catabolite repressor CREA from Aspergillus nidulans. In addition to the overall amino acid sequence relatedness between CRE1 and CREA proteins, cre1 can functionally complement the A. nidulans creAd30 mutation as assessed by repression of the alcohol dehydrogenase I gene expression. The CRE1 region carrying the two zinc fingers is also very similar to the DNA binding domains of the Saccharomyces cerevisiae glucose repressors Mig1p and Mig2p. Despite the presence in the CRE1 protein of several motifs involved in the regulation of Mig1p activity, cre1 cannot complement mig deficiencies in S. cerevisiae. These data suggest that glucose repression pathways may have evolved differently in yeasts and filamentous fungi.
Induction of p53 dependent apoptosis upon overexpression of a nuclear protein tyrosine phosphatase
Authors: Radha Vegesna , Sudhakar Ch , Swarup Ghanshyam
Published: July 2002

Two ubiquitously expressed protein tyrosine phosphatases, PTP‐S2 and PTP‐S4 (also known as TC45 and TC48, respectively), are alternately spliced products of the same gene. Overexpression of PTP‐S2 by transient transfection induced chromatin condensation and nuclear fragmentation, typical of apoptosis. Expression of PTP‐S4 resulted in a much lower number of cells with apoptotic phenotype. PTP‐S2 induced apoptosis in MCF7 and A549 human tumor cell lines which are p53 positive but not in HeLa and SW620 cells which are p53 negative. Apoptosis induced by PTP‐S2 in MCF7 cells was inhibited by cotransfection with mutant p53 (Arg‐273→His) but not by wild type p53. PTP‐S2 induced apoptosis was inhibited by antiapoptotic protein Bcl2 and certain inhibitors of caspases. These results suggest that the nuclear tyrosine phosphatase PTP‐S2 induces p53 dependent, serum starvation independent and caspase mediated apoptosis.
A capping domain for LRR protein interaction modules
Authors: Ceulemans Hugo , De Maeyer Marc , Stalmans Willy , Bollen Mathieu
Published: July 2002

Leucine‐rich repeats (LRR) are protein interaction modules which are present in a large number of proteins with diverse functions. We describe here a novel motif (16–19 residues) downstream of the last, incomplete, LRR in a subfamily of LRR proteins. In the U2A’ spliceosomal protein, this motif is folded into a cap that shields the hydrophobic core of the LRRs from the solvent. Modelling of the LRR‐cap in the imidazoline‐1 candidate receptor, using the known structure of U2A’ as template, showed a conservation of the basic structural features.
A novel ADP‐ribosylation like factor (ARL‐6), interacts with the protein‐conducting channel SEC61β subunit
Authors: Ingley E. , Williams J.H. , Walker C.E. , Tsai S. , Colley S. , Sayer M.S. , Tilbrook P.A. , Sarna M. , Beaumont J.G. , Klinken S.P.
Published: July 2002

We report here the isolation of a new member of the ADP‐ribosylation factor (ARF)‐like family (ARL‐6) present in the J2E erythroleukemic cell line, but not its myeloid variants. Consistent with this lineage‐restricted expression, ARL‐6 mRNA increased with erythropoietin‐induced maturation of J2E cells, and decreased with interleukin 6‐induced differentiation of M1 monoblastoid cells. In tissues, ARL‐6 mRNA was most abundant in brain and kidney. While ARL‐6 protein was predominantly cytosolic, its membrane association increased following exposure to GTP‐γS, like many members of the ARF/ARL family. Using the yeast two‐hybrid system, six molecules which interact with ARL‐6 were identified including SEC61β, a subunit of the heterotrimeric protein conducting channel SEC61p. Co‐immunoprecipitation of ARL‐6 confirmed a stable association between ARL‐6 and SEC61β in COS cells. These results demonstrate that ARL‐6, a novel member of the ADP‐ribosylation factor‐like family, interacts with the SEC61β subunit.
Amino‐terminal truncation of procalcitonin, a marker for systemic bacterial infections, by dipeptidyl peptidase IV (DP IV)
Authors: Wrenger S. , Kähne T. , Bohuon C. , Weglöhner W. , Ansorge S. , Reinhold D.
Published: July 2002

Increased concentrations of procalcitonin (PCT) are found in the plasma of patients with thermal injury and in patients with sepsis and severe infection, making this molecule important as a diagnostic and prognostic marker in these diseases. Interestingly, only the truncated form of PCT, PCT(3‐116), is present in the plasma of these patients. The enzyme responsible for this truncation is unknown as yet. Here, using capillary zone electrophoresis, mass spectrometry and Edman sequence analysis, we demonstrate that dipeptidyl peptidase IV (DP IV, EC 3.4.14.5) is capable of catalyzing the hydrolysis of PCT(1‐116), releasing the N‐terminal dipeptide Ala‐Pro. We hypothesize that PCT(3‐116) is the result of the hydrolysis of PCT(1‐116) by soluble DP IV of the blood plasma or by DP IV expressed on the surface of cells.
Symmetry for exterior elliptic problems and two conjectures in potential theory
Authors: Sirakov Boyan
Published: July 2002

In this paper we extend a classical result of Serrin to a class of elliptic problems

Δu+f(u,|∇u|)=0

in exterior domains

ℝ^N\setminus G

(or

Ω\setminus G

with

Ω

and

G

bounded). In case

G

is an union of a finite number of disjoint

C^2

-domains

G_i

and

u=a_i>0

,

∂u/∂n=α_i⩽0

on

∂G_i

,

u→0

at infinity, we show that if a non-negative solution of such a problem exists, then

G

has only one component and it is a ball. As a consequence we establish two results in electrostatics and capillarity theory. We further obtain symmetry results for quasilinear elliptic equations in the exterior of a ball.

Nous étendons un résultat classique de Serrin à des problèmes elliptiques

Δu+f(u,|∇u|)=0

dans des domaines extérieures du type

ℝ^N\setminus G

(où

Ω\setminus G

, avec

Ω

et

G

bornés). En supposant que

G=\bigcup^k_{i=1}G_i

, où

G_i

sont des domaines disjoints de classe

C^2

, et que

u=a_i>0

,

∂u/∂n=α_i⩽0

sur

∂G_i

,

u→0

à l’infini, nous montrons que ce problème admet une solution classique seulement si

G

a une seule composante connexe et

G

est une boule. Comme conséquence nous obtenons deux résultats sur des problèmes provenant de l’électrostatique et de la théorie de la capillarité. Nous obtenons aussi des résultats de symétrie pour des équations elliptiques quasi-linéaires dans l’extérieur d’une boule.
On the Liouville property for fully nonlinear equations
Authors: Cutrı̀ Alessandra , Leoni Fabiana
Published: July 2002

In this paper we prove some Liouville theorems for nonnegative viscosity supersolutions of a class of fully nonlinear uniformly elliptic problems in ℝN.

Dans ce travail nous démontrons des théorèmes de Liouville pour des sur-solutions de viscosité positives de problèmes uniformement elliptique complètement non linéaires dans ℝN.
Macroscopic limit of Vlasov type equations with friction
Authors: Jabin Pierre-Emmanuel
Published: July 2002

The purpose of this paper is to investigate the limit of some kinetic equations with a strong force. Due to friction, the solution concentrates to a monokinetic distribution so as to keep the total of force bounded and in the limit we recover a macroscopic system. This kind of asymptotics is a natural question when the mass of the particles is very small or their inertia is neglected. After that we also study the properties of the limit system and especially the uniqueness of solutions which provides the full convergence of the family of solutions to the kinetic equation.

Cet article se propose d’étudier la limite de solutions d’une équation cinétique avec frottement lorsque les termes de force deviennent prédominants. A cause du frottement, les solutions se concentrent progressivement en vitesse de manière à ce que la somme des forces reste bornée ; à la limite cette concentration nous oblige à remplacer l’équation cinétique par un système macroscopique. Cette problème apparait notamment quand on fait tendre vers zéro la masse des particules ou quand on néglige leur inertie. Enfin certaines propriétés du système, et particulièrement l’unicité, seront détaillées afin d’obtenir une convergence de toute la suite des solutions et pas seulement d’une suite extraite.
Ground states of semilinear elliptic equations: a geometric approach
Authors: Bamón Rodrigo , Flores Isabel , Pino Manuel del
Published: July 2002

We consider the problem

\begin{gather*}
\Delta u + u^p + u^q=0, \quad \text{in } \mathbb R^N\\
0<u(x) \to 0 \quad \text{as } |x| \to + \infty
\end{gather*}

where

1
N/(N−2)

and then let

q

approach

(N+2)/(N−2)

. If we fix

q

and then let

p

be close enough to

N/(N−2)

then no solutions exist.

On considère le problème de trouver des solutions de l’equation elliptique

\Delta u + u^p + u^q=0, \quad \text{dans } \mathbb R^N\\

avec

0<u(x) \to 0 \quad \text{lorsque } |x| \to + \infty

où

1
N/(N−2)

et

q

s’approche de

(N+2)/(N−2)

. En plus, si l’on fixe

q

et l’on prend

p

assez proche de

N/(N−2)

alors il n’existe pas de solution.
Travelling fronts for multidimensional nonlinear transport equations
Authors: Schwetlick Hartmut R
Published: July 2002

We consider a nonlinear transport equation as a hyperbolic generalisation of the well-known reaction-diffusion equation. We show the existence of strictly monotone travelling fronts for the three main types of the nonlinearity: the positive source term, the combustion law, and the bistable case.

In the first case there is a whole interval of possible speeds containing its strictly positive minimum. For subtangential nonlinearities we give an explicit expression for the minimal wave speed.

Nous considérons une équation de transport nonlinéaire comme étant une généralisation hyperbolique de l’équation de réaction-diffusion bien connue. Nous montrons l’existence de fronts progressifs strictement monotones pour les trois principaux types de la nonlinéarité: le terme source positif, la loi de combustion et le cas « bistable ». Dans le premier cas il existe tout un interval de vitesses possibles comprenant son minimum. Dans le cas de nonlinéarités « sous-tangentielles » nous donnons une expression explicite de cette vitesse minimale.
On the minimal action function of autonomous lagrangians associated to magnetic fields
Authors: Dias Carneiro M.J. , Lopes Arthur
Published: July 2002

In this paper we show the existence of a plateau for the minimal action function associated with a model for a particle under the influence of a magnetic field (Hall effect). We describe the structure of the Mather sets, that is, sets that are supports of minimizing measures for the corresponding autonomous Lagrangian.

This description is obtained by constructing a twist map induced by the first return map defined on a certain transversal section in a fixed level of energy.

Dans cet article nous démontrons l’existence d’un plateau pour la fonction d’action minimale associée au modèle du mouvement d’une particule sous l’action d’un champ magnétique (Hall effect). Nous décrivons la structure des ensembles de Mather, c’est-à-dire, les ensembles qui sont le support des mesures minimisantes pour le Lagrangian autonome correspondant.

Cette description est obtenue en construisant une application « twist å induite par l’application de premier retour définie sur une section transverse dans chaque niveau d’énergie.
Hyperbolic characteristics on star-shaped hypersurfaces
Authors: Liu Chun-gen , Long Yiming
Published: July 2002

In this paper, we study the stability of closed characteristics on a starshaped compact smooth hypersurface

Σ

in

ℝ^{2n}

. We show that the Maslov-type mean index of such a closed characteristic is independent of the choice of the Hamiltonian functions, and prove that on

Σ

either there are infinitely many closed characteristics, or there exists at least one nonhyperbolic closed characteristic, provided every closed characteristic possesses its Maslov-type mean index greater than

2

when

n

is odd, and greater than

1

when

n

is even.

Soit

Σ

une hypersurface étoilée compacte,

C^2

, dans

ℝ^{2n}

, qui est obtenue par la méthode de variation directe. Dans cet article, nous étudions la stabilité des caractéristiques fermées sur

Σ

. Nous démontrons que l’indice moyen de type de Maslov d’une telle caractéristique fermée ne dépend pas du choix des fonctions Hamiltoniennes. Si on suppose qu’il n’existe qu’un nombre fini de caractéristiques fermées, alors il existe au moins une caractéristique fermée nonhyperbolique sur

Σ

si pour toute caractéristique fermée sur

Σ

, son indice moyen de type de Maslov est supérieur à

2

, et si

n

est impair (resp.

1

, et si

n

est pair).
Partial regularity results for minimizers of quasiconvex functionals of higher order
Authors: Kronz Manfred
Published: July 2002

We consider minimizers

u \in W^{m,p}\left(\Omega ,ℝ^{N}\right)

of uniformly strictly quasiconvex functionals

F\left(u\right) = \int _{\Omega }f\left(D^{m}u\right)d\mathcal L^{n}

of higher order. Here

Ω

is a domain in

ℝ^{n}

,

m⩾1

, and

f

is a

C^2

-integrand with growth of order

p

,

p⩾2

. Using the technique of harmonic approximation we give a direct proof of almost everywhere

C^{m,α}

-regularity for such minimizers.

Nous étudions des minimiseurs

u \in W^{m,p}\left(\Omega ,ℝ^{N}\right)

des fonctionnelles

F\left(u\right) = \int _{\Omega }f\left(D^{m}u\right)d\mathcal L^{n}

uniformément strictement quasiconvexes du ordre

2m

,

m⩾1

. Ici,

Ω ⊂ ℝ^n

est une domaine et

f

est une fonction de classe

C^2

avec une crossance du ordre

p

,

p⩾2

. À l'aide de la technique d'approximation harmonique nous obtenons une preuve directe pour la regularité de classe

C^{m,α}

pour les minimiseurs dans un ensemble ouvert

\widetilde \Omega \subset \Omega

avec

\mathcal L^{n}(\Omega \backslash \widetilde \Omega) = 0

.
Homogenization of a quasi-linear problem with quadratic growth in perforated domains: An example
Authors: Casado-Díaz Juan
Published: July 2002

We study the homogenization of Dirichlet problems for a fixed quasi-linear operator which is the perturbation of the Laplace operator by the square of the gradient, when the domain varies arbitrarily. With respect to the Dirichlet problem for the linear Laplace operator posed on the same domains, a new nonlinear zeroth order term appears in the homogenized problem. We also give a corrector result.

On étudie l’homogénéisation de problèmes de Dirichlet pour un opérateur quasi-linéaire fixe qui est la perturbation de l’opérateur de Laplace par le carré du gradient, pour une suite de domaines qui varient arbitrairement. Par rapport au problème de Laplace avec des conditions de Dirichlet posé sur les mêmes domaines, il apparaît un nouveau terme non-linéaire d’ordre zéro dans le problème homogénéisé. On obtient aussi un résultat de correcteur.
Minimizing a functional depending on $\nabla u$ and on $u$
Authors: Cellina Arrigo
Published: July 2002

We prove existence of solutions for a class of minimum problems of the Calculus of Variations, where the integrand depends both on

\nabla u

and on

u

.

On donne un théorème d’existence de solutions pour un problème du calcul des variations ou la fonctionnelle dépend de

u

et de

\nabla u

.
Uniqueness and asymptotic behavior of solutions with boundary blow-up for a class of nonlinear elliptic equations
Authors: Marcus M. , Véron L.
Published: July 2002

We study the uniqueness and expansion properties of the positive solutions

u

of

(E)

Δu + hu − ku^p = 0

in a non-smooth domain

Ω

, subject to the condition

u(x) → ∞

when

\operatorname{dist} (x, ∂Ω) → 0

, where

h

and

k

are continuous functions in

\overline\Omega

,

k > 0

and

p > 1

. When

∂Ω

has the local graph property, we prove that the solution is unique. When

∂Ω

has a singularity of conical or wedge-like type, we give the asymptotic behavior of

u

. When

∂Ω

has a re-entrant cuspidal singularity, we prove that the rate of blow-up may not be of the same order as in the previous more regular cases.

Nous étudions les propriétés d’unicité et de comportement limite des solutions positives

u

de

(E)

Δu + hu − ku^p = 0

dans un domaine non régulier

Ω

, sujettes à la condition

u(x) → ∞

quand

\operatorname{dist} (x, ∂Ω) → 0

, où

h

et

k

sont des fonctions continues dans

\overline\Omega

,

k > 0

et

p > 1

. Quand

∂Ω

a la propriété du graphe local, nous démontrons que la solution est unique. Quand

∂Ω

a une singularité de type conique ou dièdrale, nous donnons le comportement asymptotique de

u

. Quand

∂Ω

a une singularité cuspide rentrante, nous montrons que l’ordre de l’explosion peut ne pas être le même que dans les cas précédents.
Regularity at the free boundary of two-dimensional stationary harmonic maps
Authors: Grüter Michael
Published: July 2002

It is shown that the regularity problem at the free boundary of two-dimensional stationary harmonic maps can be reduced to the corresponding problem for two-dimensional minimal surfaces and that the analogous regularity results hold true.

On montre que le problème de la régularitéà la frontière libre d’une application harmonique stationnaire bidimensionnelle peut être réduit au problème analogue pour les surfaces minimales, et que les résultats de régularité correspondants sont encore vrais.
Saddle-focus singular cycles and prevalence of hyperbolicity
Authors: San Martín Bernardo
Published: July 2002

The objective of this work is to study the 2-parameter unfolding of an intricate bifurcating dynamical structure in dimension 3, namely a saddle-focus singular cycle. It is showed that hyperbolicity is a prevalent phenomena: the initial system is a total density point of hyperbolic dynamics. This dynamic exhibit either simple critical elements or nontrivial basic set. It seems to be the first time that non-trivial hyperbolicity (as well as its prevalence) is proved for the maximal invariant set for a perturbation of a vector field with a cycle containing a saddle-focus singularity.

L’objectif de ce travail est l’étude du développement à 2 paramètres d’une structure dynamique complexe avec bifurcation en dimension 3, à savoir un cycle singulier « selle-foyer å. Nous montrons que l’hyperbolicité est un pénomène prévalant : le système initial est un point de densité totale de dynamiques hyperboliques. Cette dynamique présente ou bien des éléments critiques simples ou un ensemble fondamental non trivial. Cela semble le premier ensemble où l’hyperbolicité non triviale (et sa prévalence) est prouvée pour l’ensemble invariant maximal pour une perturbation d’un champ vecteur à un cycle contenant une singularité « selle-foyer å.