Serine Phosphorylation of Insulin Receptor Substrate 1 by Inhibitor κB Kinase Complex

摘要: Insulin resistance contributes importantly to the pathophysiology of type 2 diabetes mellitus. One mechanism mediating insulin may involve phosphorylation serine residues in receptor substrate-1 (IRS-1), leading impairment ability IRS-1 activate downstream phosphatidylinositol 3-kinase-dependent pathways. Insulin-resistant states and are associated with activation inhibitor κB kinase (IKK) complex. However, precise molecular mechanisms by which IKK contribute development not well understood. In this study, using phosphospecific antibodies against rat phosphorylated at Ser307 (equivalent Ser312 human IRS-1), we observed response TNF-α or calyculin A treatment that paralleled surrogate markers for activation. The tumor necrosis factor-α was significantly reduced cells pretreated 15 deoxy-prostaglandin J2 as derived from knock-out mice. We interactions between endogenous intact a co-immunoprecipitation approach. Moreover, interaction basal state upon increased IRS-1. Data vitro assays recombinant substrate were consistent function direct multiple sites addition Ser312. Taken together, our data suggest is novel (and other sites) mediated inflammatory