Human growth factor receptor bound 14 binds the activated insulin receptor and alters the insulin-stimulated tyrosine phosphorylation levels of multiple proteins

dc.contributor.authorHemming, R
dc.contributor.authorAgatep, R
dc.contributor.authorBadiani, K
dc.contributor.authorWyant, K
dc.contributor.authorArthur, G
dc.contributor.authorGietz, RD
dc.contributor.authorTriggs-Raine, B
dc.date.accessioned2007-10-05T16:08:15Z
dc.date.available2007-10-05T16:08:15Z
dc.date.issued2001-02-28
dc.description.abstractTo identify proteins interacting in the insulin-signaling pathway that might define new pathways or regulate existing ones, we have employed the yeast two-hybrid system. In a two-hybrid screen of a human liver cDNA library, we identified the human growth factor receptor bound 14 (hGrb14) adaptor protein as a partner of the activated insulin receptor. Additional analysis of the insulin receptor - hGrb14 interaction in the yeast two-hybrid system revealed that the SH2 domain of hGrb14 was not the sole region involved in binding the activated insulin receptor. The insulin-stimulated interaction between hGrb14 and the insulin receptor was also observed in different mammalian cultured cell lines. This association was detected at 1 min of insulin stimulation and was maximal at 10 nM and greater concentrations of insulin. Chinese hamster ovary cells stably expressing the insulin receptor (CHO-IR) and hGrb14 were used to examine the effects of hGrb14 overexpression on insulin-stimulated tyrosine phosphorylation of proteins; in general, increasing levels of hGrb14 expression resulted in a reduction in tyrosine phosphorylation. This decrease was demonstrated for the specific proteins src homology-containing and collagen-related protein (Shc), insulin receptor substrate-1 (IRS-1), and Downstream of tyrosine Kinase (Dok). The broad effects of hGrb14 overexpression on insulin-stimulated tyrosine phosphorylation suggest that it acts early in the insulin-signaling pathway.en
dc.format.extent1517037 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.citation0829-8211; BIOCHEM CELL BIOL, FEB 2001, vol. 79, no. 1, p.21 to 32.en
dc.identifier.urihttp://hdl.handle.net/1993/2898
dc.language.isoengen_US
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dc.rightsopen accessen_US
dc.statusPeer revieweden
dc.subjectinsulin signalingen
dc.subjectgrowth factor receptor bound 14en
dc.subjectGrb14en
dc.subjectadaptor proteinen
dc.subjectinsulin receptoren
dc.subjectFACTOR-I RECEPTORen
dc.subjectHIGH-EFFICIENCY TRANSFORMATIONen
dc.subjectSRC HOMOLOGY-2 DOMAINen
dc.subjectSH2 DOMAINen
dc.subjectPLECKSTRIN HOMOLOGYen
dc.subjectESCHERICHIA-COLIen
dc.subject2-HYBRID SYSTEMen
dc.subjectADAPTER PROTEINen
dc.subjectKINASE DOMAINen
dc.subjectGRB-IRen
dc.titleHuman growth factor receptor bound 14 binds the activated insulin receptor and alters the insulin-stimulated tyrosine phosphorylation levels of multiple proteinsen
dc.typejournal articleen_US
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