Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Receptor tyrosine phosphatases (R-PTPases) feature PTPase domains in the context of a receptor-like transmembrane topology. The R-PTPase R-PTP-kappa displays an extracellular domain composed of fibronectin type III motifs, a single immunoglobulin domain, as well as a recently defined MAM domain (Y.-P. Jiang, H. Wang, P. D'Eustachio, J.M. Musacchio, J. Schlessinger, and J. Sap, Mol. Cell. Biol. 13:2942-2951, 1993). We report here that R-PTP-kappa can mediate homophilic intercellular interaction. Inducible expression of the R-PTP-kappa protein in heterologous cells results in formation of stable cellular aggregates strictly consisting of R-PTP-kappa-expressing cells. Moreover, the purified extracellular domain of R-PTP-kappa functions as a substrate for adhesion by cells expressing R-PTP-kappa and induces aggregation of coated synthetic beads. R-PTP-kappa-mediated intercellular adhesion does not require PTPase activity or posttranslational proteolytic cleavage of the R-PTP-kappa protein and is calcium independent. The results suggest that R-PTPases may provide a link between cell-cell contact and cellular signaling events involving tyrosine phosphorylation.
Mol Cell Biol 1994 Jan
PMID:Receptor tyrosine phosphatase R-PTP-kappa mediates homophilic binding. 826 77

We describe a new member of the receptor protein tyrosine phosphatase family, R-PTP-kappa, cDNA cloning predicts that R-PTP-kappa is synthesized from a precursor protein of 1,457 amino acids. Its intracellular domain displays the classical tandemly repeated protein tyrosine phosphatase homology, separated from the transmembrane segment by an uncharacteristically large juxta-membrane region. The extracellular domain of the R-PTP-kappa precursor protein contains an immunoglobulin-like domain and four fibronectin type III-like repeats, preceded by a signal peptide and a region of about 150 amino acids with similarity to the Xenopus A5 antigen, a putative neuronal recognition molecule (S. Takagi, T. Hsrata, K. Agata, M. Mochii, G. Eguchi, and H. Fujisawa, Neuron 7:295-307, 1991). Antibodies directed against the intra- and extracellular domains reveal that the R-PTP-kappa precursor protein undergoes proteolytic processing, following which both cleavage products remain associated. By site-directed mutagenesis, the likely cleavage site was shown to be a consensus sequence for cleavage by the processing endopeptidase furin, located in the fourth fibronectin type III-like repeat. In situ hybridization analysis indicates that expression of R-PTP-kappa in the central nervous system is developmentally regulated, with highest expression seen in actively developing areas and, in the adult, in areas capable of developmental plasticity such as the hippocampal formation and cerebral cortex. The mouse R-PTP-kappa gene maps to chromosome 10, at approximately 21 centimorgans from the centromere.
Mol Cell Biol 1993 May
PMID:Cloning and characterization of R-PTP-kappa, a new member of the receptor protein tyrosine phosphatase family with a proteolytically cleaved cellular adhesion molecule-like extracellular region. 847 52

Tyrosine phosphorylation of proteins plays an important role in cellular signaling and many cellular activities. The levels of cellular phosphorylation are reversibly controlled by protein tyrosine kinases and protein tyrosine phosphatases. The murine R-PTP-kappa, a receptor-type protein tyrosine phosphatase, has recently been cloned (Jiang et al. (1993) Mol. Cell. Biol. 13, 2942-2951). In order to identify the protein tyrosine phosphatases critical to the cellular signal transduction in human keratinocytes, a polymerase chain reaction (PCR)-based strategy was employed, and we have cloned a human homologue of the murine R-PTP-kappa. Here, we report the isolation of a complementary DNA encoding a human R-PTP-kappa. Of the several overlapping cDNA clones, one clone, which we originally termed p55-7, was found to encode a transmembrane protein of 1440 amino acids and was highly conserved with murine R-PTP-kappa with 98% identity at the amino-acid levels. The human R-PTP-kappa gene was localized to chromosome 6 by southern hybridization of DNA from a rodent/human somatic cell mapping panel. Northern blot analysis of RNA from several human tissues revealed, like the murine R-PTP-kappa, the presence of a major mRNA of approx. 7.0 kb and a minor mRNA of approx. 5.3 kb. In contrast to the expression of murine R-PTP-kappa which was highly expressed in liver and kidney, the human R-PTP-kappa was predominantly expressed in spleen, prostate, and ovary. However, the transcripts were detectable at various levels in all examined tissues (thymus, testis, small intestine, and colon) except for PBL (peripheral blood leukocytes). In addition, human R-PTP-kappa displayed a restricted pattern of expression among a series of cell lines, and was apparently expressed in an epidermal cells and cell lines (human normal keratinocytes, HaCaT, and A431), but was not detectable in other cell lines tested after longer exposure.
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PMID:Molecular cloning and chromosomal localization of a human gene homologous to the murine R-PTP-kappa, a receptor-type protein tyrosine phosphatase. 904 48

Receptor protein tyrosine phosphatases (RPTPs) comprise a family of proteins that feature intracellular phosphatase domains and an ectodomain with putative ligand-binding motifs. Several RPTPs are expressed in the brain, including RPTP-kappa which participates in homophilic cell-cell interactions in vitro [Y.-P. Jiang, H. Wang, P. D'Eustachio, J.M. Musacchio, J. Schlessinger, J. Sap, Cloning and characterization of R-PTP-kappa, a new member of the receptor protein tyrosine phosphatase family with a proteolytically cleaved cellular adhesion molecule-like extracellular region, Mol. Cell. Biol. 13 (1993) 2942-2951; J. Sap, Y.-P. Jiang, D. Friedlander, M. Grumet, J. Schlessinger, Receptor tyrosine phosphatase R-PTP-kappa mediates homophilic binding, Mol. Cell. Biol. 14 (1994) 1-9]. The homology of RPTP-kappa's ectodomain to neural cell adhesion molecules indicates potential roles in developmental processes such as axonal growth and target recognition, as has been demonstrated for certain Drosophila RPTPs. The brain distribution of RPTP-kappa-expressing cells has not been determined, however. In a gene-trap mouse model with a beta-gal+neo (beta-geo) insertion in the endogenous RPTP-kappa gene, the consequent loss of RPTP-kappa's enzymatic activity does not produce any obvious phenotypic defects [W.C. Skarnes, J.E. Moss, S.M. Hurtley, R.S.P. Beddington, Capturing genes encoding membrane and secreted proteins important for mouse development, Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 6592-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells throughout the CNS that display RPTP-kappa promoter activity. Several neural systems highly expressed the transgene-most notably cortical, olfactory, hippocampal, hypothalamic, amygdaloid and visual structures. These well-characterized brain regions may provide a basis for future studies of RPTP-kappa function.
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PMID:Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse. 1022 93

The resumption of oocyte meiosis is a critical step for the progression of oocyte development, which requires an intimate collaboration of a variety of hormones and growth factors. Insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) family are well recognized to promote oocyte maturation. However, the mechanism by which they coordinate this process remains unknown. The present study demonstrated that IGF-I can increase egfr mRNA and protein levels in follicle cell culture or intact follicles. This stimulation can be significantly inhibited by IGF-IR specific inhibitor, NVP-ADW742. The inhibitors against phosphatidylinositol-3-kinase (PI3K), phosphoinositide-dependent protein kinase 1 (PDK1) and Akt also dramatically abolished IGF-I-induced egfr expression, suggesting that the classical PI3K/Akt pathway mediated the action of IGF-I in this regulation. We further found that not only was the protein level of Egfr increased, but also the phosphorylation level was enhanced by IGF-I. Unlike egfr, IGF-I failed to stimulate the expression of Egf-like ligands whereas decreased the level of protein-tyrosine phosphatase, receptor type, kappa (ptprk), a protein tyrosine phosphatase. The oocyte maturation assay further confirmed that IGF-I initiates this regulation through its cognate receptor in the follicle cells. Taken together, IGF-I promoted oocyte maturation, in part at least, through Egf-like ligands/Egfr pathway. This study sheds light on the cross-talk between two important growth factors in the zebrafish ovary and the mechanism underlying the IGF-I induction on oocyte maturation.
Mol Cell Endocrinol 2016 Jan 05
PMID:Insulin-like growth factor I promotes oocyte maturation through increasing the expression and phosphorylation of epidermal growth factor receptor in the zebrafish ovary. 2659 86