The insulin receptor is a transmembrane receptor that belongs to the tyrosine kinase receptors class. It is a heterotetrameric glycoprotein composed of disulfide-linked subunits in a â-á-á-â configuration. This transmembrane receptor consists of 95kDa â-subunit, a single transmembrane domain, and 135kDa á-subunit, which is completely extracellular. Binding of insulin to the receptor results in stimulation of its intrinsic kinase activity. The insulin receptor mediates insulin action through the phosphorylation of substrate proteins. Insulin receptor becomes phosphorylated as a response to stimulation of cells by insulin, insulin-like growth factor (IGF-I) and interleukin 4. The major substrates of the insulin receptor kinase are the insulin receptor substrate (IRS) family of proteins, IRS-1, IRS-2, IRS-3, IRS-4. Recently, two more signaling proteins, IRS5/DOK4 and IRS6/DOK5, have been identified as potentially new members of the IRS family. The insulin receptor substrate-1 (IRS-1), a 170-185 kDa protein, is a major substrate of the insulin receptor. IRS-1 is phosphorylated on serine, threonine and tyrosine residues in a variety of tissues.
