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Absence of IQGAP1 Protein Leads to Insulin Resistance.

Authors :
Chawla, Bhavna
Hedman, Andrew C.
Sayedyahossein, Samar
Erdemir, Huseyin H.
Zhigang Li
Sacks, David B.
Source :
Journal of Biological Chemistry. 2/24/2017, Vol. 292 Issue 8, p3273-3289. 17p.
Publication Year :
2017

Abstract

Insulin binds to the insulin receptor (IR) and induces tyrosine phosphorylation of the receptor and insulin receptor substrate-1 (IRS-1), leading to activation of the PKB/Akt and MAPK/ERK pathways. IQGAP1 is a scaffold protein that interacts with multiple binding partners and integrates diverse signaling cascades. Here we show that IQGAP1 associates with both IR and IRS-1 and influences insulin action. In vitro analysis with pure proteins revealed that the IQ region of IQGAP1 binds directly to the intracellular domain of IR. Similarly, the phosphotyrosine-binding domain of IRS-1 mediates a direct interaction with the C-terminal tail of IQGAP1. Consistent with these observations, both IR and IRS-1 co-immunoprecipitated with IQGAP1 from cells. Investigation of the functional effects of the interactions revealed that in the absence of IQGAP1, insulin-stimulated phosphorylation of Akt and ERK, as well as the association of phosphatidylinositol 3-kinase with IRS-1, were significantly decreased. Importantly, loss of IQGAP1 results in impaired insulin signaling and glucose homeostasis in vivo. Collectively, these data reveal that IQGAP1 is a scaffold for IR and IRS-1 and implicate IQGAP1 as a participant in insulin signaling. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219258
Volume :
292
Issue :
8
Database :
Academic Search Index
Journal :
Journal of Biological Chemistry
Publication Type :
Academic Journal
Accession number :
121478839
Full Text :
https://doi.org/10.1074/jbc.M116.752642