Insulin Receptor (IR) is a transmembrane receptor tyrosine kinase which, upon insulin binding, initiates a cascade of events, including autophosphorylation, phosphorylation of cellular protein substrates, glucose transport, and glycogen synthesis. IR is synthesized as a large glycosylated precursor that is cleaved upon maturation into a 130 kDa α-subunit with kinase activity and a 95 kDa β-subunit. The active Insulin Receptor is a heterotetramer of homologus α and β subunits joined by disulfide bonds. Among the major cytosolic substrates of the Insulin Receptor are IRS-1 and -2, β-Adrenergic receptor, and pp15 (adipocyte lipid-binding protein, ALBP). Autophosphorylation of the IR recruits IRS-1 and -2 to the phosphotyrosines. Subsequently, the phosphorylated IRS-1 and -2 act as docking sites for other signaling proteins like PI3-Kinase, Shc, PTP1D, Nck, etc. In addition, the phosphatase LAR is tightly associated with the IR and LAR becomes activated after insulin stimulation dephosphorylating the IR and its substrates. Therefore, LAR provides a turn-off mechanism in insulin signaling.
This antibody is routinely tested by western blot analysis. Other applications were tested at BD Biosciences Pharmingen during antibody development only or reported in the literature.