Sequestosome 1/p62 and TRAF6 serve as a bridge to connect IRS-1 with Akt in insulin signaling

Abstract

Abnormalities in the insulin-signaling pathway might result in insulin resistance, contributing to the development of type 2 diabetes. Previous studies have established the involvement of p62 in the insulin-signaling pathway through its association with IRS-1 and the interaction of p62 with TRAF6. Studies conducted using L6 myotubes and the transfection of CHO/ IR cells indicated that IRS-1, p62, Akt and TRAF6 interact upon insulin stimulation. The interaction between p62 and Akt is impaired in TRAF6 knockout and p62 knockout Mouse Embryonic Fibroblast cells, confirming that TRAF6 connects p62 with Akt. Further, the transfection of ASp62 in CHO/ IR cells provided evidence that TRAF6 interacts with Akt but not with IRS-1 upon the reduction of p62 expression. In p62 knockout, IRS-1 does not interact with TRAF6 and Akt whereas in TRAF6 knockout, IRS-1 interacts with p62 but not Akt. Overall, these results demonstrate that p62 and TRAF6 link IRS-1 with Akt implying the existence of these proteins as a complex in the insulin signaling pathway.