Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA sequences encoding a novel member of the receptor protein tyrosine phosphatase (R-PTP) family, termed PCP-2, were identified in a human pancreatic adenocarcinoma cDNA library. Human PCP-2 cDNA predicts a protein of 1430 amino acids with a calculated Mr of 160 kDa. The predicted PCP-2 enzyme consists of a 740 amino acid extracellular region, a single transmembrane domain, and a 666 amino acid intracellular portion. The extracellular sequence contains a MAM (meprin/A5/PTPmu) domain, an immunoglobulin-like domain and four fibronectin type III-like repeats, suggesting that it is a member of the PTPkappa and PTPmu subfamily. The intracellular region contains two tandemly-repeated protein tyrosine phosphatase domains. Northern blot analyses revealed a single transcript of 5.5 kilobases, which is expressed at different levels in many human tissues except spleen and placenta. Upon transfection of PCP-2 cDNA into human embryonic kidney fibroblast 293 cells, a protein with an apparent Mr of 180 000 was detected by immunoblot analysis. This size was reduced to the predicted Mr upon treatment with endoglycosidase F, indicating that PCP-2 is glycosylated and, hence, expressed at the cell surface. A potential role of PCP-2 in cell-cell recognition and adhesion is supported by its co-localization with cell adhesion molecules, such as catenin and E-cadherin, at sites of cell-cell contact.
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PMID:Characterization of PCP-2, a novel receptor protein tyrosine phosphatase of the MAM domain family. 870 May 14

Receptor protein tyrosine phosphatases (RPTPs) are structurally characterized by the diversity of their extracellular domains (ECDs). These domains display Ig-like, fibronectin type III (FNIII), MAM (meprin, A5, PTPmu), and carbonic anhydrase (CAH) motifs that resemble those present in many cell adhesion molecules (CAMs). However, in contrast to most CAMs, RPTPs also contain an intracellular domain possessing phosphatase activity. This combination makes RPTPs unusual in their ability to directly couple extracellular adhesion mediated events to intracellular signaling pathways. Even though identifying physiologically relevant ligands for RPTPs has proven difficult, recent experiments have shown that RPTPs can bind to themselves (homophilic) as well as to other proteins (heterophilic). For example, the type IIb RPTP, PTPmu? acts as a homophilic cell adhesion protein for epithelial and neural cells while the type V RPTP, PTPbeta/zeta binds a variety of CAMs and ECM components such as N-CAM and pleiotrophin. Interestingly, both PTPmu and PTPbeta/zeta interact with and regulate the tyrosine phosphorylation level of catenins, which are critical in physiological and pathological events such as cell migration, adhesion and transformation. In addition to their role as CAMs, RPTPs directly interact with intracellular adhesion regulators such as the cadherin/catenin complex, p130cas and GIT1. In summary, RPTPs represent a diverse family of transmembrane proteins that act as adhesion receptors and directly translate this engagement into intracellular signaling by modulating phosphotyrosine levels. Discovering the specific roles of RPTPs as receptors and identifying their ligands may lead to a better understanding of human illnesses whose underlying mechanisms involve cellular adhesion.
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PMID:Receptor protein tyrosine phosphatases as mediators of cellular adhesion. 1245 40

Type IIB receptor protein tyrosine phosphatases (RPTPs) are bi-functional cell surface molecules. Their ectodomains mediate stable, homophilic, cell-adhesive interactions, whereas the intracellular catalytic regions can modulate the phosphorylation state of cadherin/catenin complexes. We describe a systematic investigation of the cell-adhesive properties of the extracellular region of RPTPmu, a prototypical type IIB RPTP. The crystal structure of a construct comprising its N-terminal MAM (meprin/A5/mu) and Ig domains was determined at 2.7 A resolution; this assigns the MAM fold to the jelly-roll family and reveals extensive interactions between the two domains, which form a rigid structural unit. Structure-based site-directed mutagenesis, serial domain deletions and cell-adhesion assays allowed us to identify the four N-terminal domains (MAM, Ig, fibronectin type III (FNIII)-1 and FNIII-2) as a minimal functional unit. Biophysical characterization revealed at least two independent types of homophilic interaction which, taken together, suggest that there is the potential for formation of a complex and possibly ordered array of receptor molecules at cell contact sites.
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PMID:Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion. 1645 43