Role of Pleckstrin Homology Domain in Regulating Membrane Targeting and Metabolic Function of Insulin Receptor Substrate 3

摘要: The insulin receptor phosphorylates substrate (IRS) proteins on multiple tyrosine residues that act as docking sites to recruit a number of downstream signaling molecules. Here we show IRS3 is localized both at the plasma membrane and in nucleus. Interestingly, nuclear localization protein restricted specific regions involved mRNA processing known speckles. By using different truncated versions protein, demonstrate pleckstrin homology (PH) domain level To our knowledge this first report PH responsible for targeting host protein. site-directed mutagenesis, identify within critical proper IRS3. Mutations preventing intracellular result an inhibition IRS3-induced glucose uptake. We conclude required and, furthermore, it has key role metabolic functions In particular, data suggest nucleus two cooperative mechanisms involving domain.