Rabbit polyclonal antibody to IRS~1 (phospho~Y612)

IRS~1, a major substrate of the insulin receptor, is phosphorylated in response to stimulation of cells by insulin, insulin~like growth factor 1 (IGF~1) and interleukin 4 (IL~4). IRS~1 is phosphorylated on serine, threonine and tyrosine residues in a variety of tissues. An insulin~sensitive serine/threonine kinase casein kinase II mediates a portion of the insulin~stimulated serine/threonine phosphorylation of overexpressed IRS~1 in vivo. Thr 502 is identified as the major casein kinase II~catalyzed phosphorylation site in rat IRS~1, and Ser 99 is an additional phosphorylation site catalyzed by casein kinase II. Thus, casein kinase II~catalyzed phosphorylation of IRS~1 may be a component of the intracellular insulin signaling cascade. IRS~1 contains three putative binding sites for 14~3~3 (Ser 270, Ser 374 and Ser 641) and the motif around Ser 270 is located in the phosphortyrosine binding domain of IRS~1, which is responsible for the interaction with the insulin receptor.