Human growth factor receptor bound 14 binds the activated insulin receptor and alters the insulin-stimulated tyrosine phosphorylation levels of multiple proteins
dc.contributor.author | Hemming, R | |
dc.contributor.author | Agatep, R | |
dc.contributor.author | Badiani, K | |
dc.contributor.author | Wyant, K | |
dc.contributor.author | Arthur, G | |
dc.contributor.author | Gietz, RD | |
dc.contributor.author | Triggs-Raine, B | |
dc.date.accessioned | 2007-10-05T16:08:15Z | |
dc.date.available | 2007-10-05T16:08:15Z | |
dc.date.issued | 2001-02-28 | |
dc.description.abstract | To 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.extent | 1517037 bytes | |
dc.format.mimetype | application/pdf | |
dc.identifier.citation | 0829-8211; BIOCHEM CELL BIOL, FEB 2001, vol. 79, no. 1, p.21 to 32. | en |
dc.identifier.uri | http://hdl.handle.net/1993/2898 | |
dc.language.iso | eng | en_US |
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dc.rights | open access | en_US |
dc.status | Peer reviewed | en |
dc.subject | insulin signaling | en |
dc.subject | growth factor receptor bound 14 | en |
dc.subject | Grb14 | en |
dc.subject | adaptor protein | en |
dc.subject | insulin receptor | en |
dc.subject | FACTOR-I RECEPTOR | en |
dc.subject | HIGH-EFFICIENCY TRANSFORMATION | en |
dc.subject | SRC HOMOLOGY-2 DOMAIN | en |
dc.subject | SH2 DOMAIN | en |
dc.subject | PLECKSTRIN HOMOLOGY | en |
dc.subject | ESCHERICHIA-COLI | en |
dc.subject | 2-HYBRID SYSTEM | en |
dc.subject | ADAPTER PROTEIN | en |
dc.subject | KINASE DOMAIN | en |
dc.subject | GRB-IR | en |
dc.title | Human growth factor receptor bound 14 binds the activated insulin receptor and alters the insulin-stimulated tyrosine phosphorylation levels of multiple proteins | en |
dc.type | journal article | en_US |