Abstract 2127 RSK1 Regulation of Insulin Signaling and Glucose Metabolism in Breast Cancer

Insulin signaling regulates cell growth, proliferation and most notably, glucose uptake. Insulin Receptor Substrate 1 (IRS1), is an adaptor protein that mediates the cytoplasmic effects of insulin binding to the insulin receptor. Several signaling pathways converge on IRS1 to act as positive and negative regulators of the tightly controlled insulin signaling. Phosphorylation of IRS1 on multiple serine and threonine residues inhibits insulin signaling. Specifically, IRS1 serine 307 (S307) has been previously shown to be phosphorylated by the mechanistic target of rapamycin (mTOR) and the 40S ribosomal S6 kinase 1 (S6K1) to inhibit IRS1 function, and thus control insulin signaling through negative feedback.