| First Author | Chawla B | Year | 2017 |
| Journal | J Biol Chem | Volume | 292 |
| Issue | 8 | Pages | 3273-3289 |
| PubMed ID | 28082684 | Mgi Jnum | J:241083 |
| Mgi Id | MGI:5897710 | Doi | 10.1074/jbc.M116.752642 |
| Citation | Chawla B, et al. (2017) Absence of IQGAP1 Protein Leads to Insulin Resistance. J Biol Chem 292(8):3273-3289 |
| abstractText | 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. |
