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.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.identifier.citation0829-8211; BIOCHEM CELL BIOL, FEB 2001, vol. 79, no. 1, p.21 to 32.en
dc.rightsNo part of the NRC Research Press electronic journals may be reproduced, stored, or transmitted in any form or by any means, without the written permission of the publisher, except as stated below. Under the Canadian Copyright Act, individuals may download or print single copies of articles for personal research or study. Any person may reproduce short excerpts from articles in the journals for any purpose that respects the moral rights of authors, provided that the source is fully acknowledged. As a courtesy, the consent of authors of such material should be obtained directly from the author. Authorization to reproduce items for other than personal research or study, as stated above, may be obtained via Access © upon payment of the copyright fee of $10.00 per copy. NRC Research Press also extends certain additional rights to authors. The above rights do not extend to copying or reproduction for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale. For such copying or reproduction, arrangements must be made with NRC Research Press.en
dc.rightsopen accessen_US
dc.statusPeer revieweden
dc.subjectinsulin signalingen
dc.subjectgrowth factor receptor bound 14en
dc.subjectadaptor proteinen
dc.subjectinsulin receptoren
dc.subjectSH2 DOMAINen
dc.subject2-HYBRID SYSTEMen
dc.subjectKINASE DOMAINen
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