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http://purl.uniprot.org/citations/11018022http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11018022http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11018022http://www.w3.org/2000/01/rdf-schema#comment"Insulin receptor substrate-1 (IRS-1) protein is a major substrate of the insulin receptor tyrosine kinase and is essential for transducing many of the biological effects of insulin including mitogenesis, gene expression, and glucose transport. The N terminus of IRS-1 contains a pleckstrin homology (PH) domain that is critical for recognition and subsequent phosphorylation of IRS-1 by the activated insulin receptor. Here we report the isolation of a novel protein, PHIP (PH-interacting protein), which selectively binds to the PH domain of IRS-1 in vitro and stably associates with IRS-1 in vivo. Importantly, mutants of the IRS-1 PH domain that disrupt the PH fold fail to bind to PHIP. Anti-phosphotyrosine immunoblots of PHIP revealed no discernible insulin receptor-regulated phosphorylation, suggesting that PHIP is not itself a substrate of the insulin receptor. In contrast to full-length PHIP, overexpression of the PH-binding region of PHIP has a pronounced inhibitory effect on insulin-induced IRS-1 tyrosine phosphorylation levels. Furthermore, expression of this dominant-negative PHIP mutant leads to a marked attenuation of insulin-stimulated mitogen-activated protein kinase activity. We conclude that PHIP represents a novel protein ligand of the IRS-1 PH domain that may serve to link IRS-1 to the insulin receptor."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.org/dc/terms/identifier"doi:10.1074/jbc.c000611200"xsd:string
http://purl.uniprot.org/citations/11018022http://purl.org/dc/terms/identifier"doi:10.1074/jbc.c000611200"xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/author"Yin X."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/author"Yin X."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/author"Cheng A.M."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/author"Cheng A.M."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/author"Farhang-Fallah J."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/author"Farhang-Fallah J."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/author"Rozakis-Adcock M."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/author"Rozakis-Adcock M."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/author"Trentin G."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/author"Trentin G."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/pages"40492-40497"xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/pages"40492-40497"xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/title"Cloning and characterization of PHIP, a novel insulin receptor substrate-1 pleckstrin homology domain interacting protein."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/title"Cloning and characterization of PHIP, a novel insulin receptor substrate-1 pleckstrin homology domain interacting protein."xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/volume"275"xsd:string
http://purl.uniprot.org/citations/11018022http://purl.uniprot.org/core/volume"275"xsd:string