Post-translational modifications of the insulin receptor.

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The full program for expression of insulin’s action is contained in a locus on the cell surface, the insulin receptor (1,2). During the last decade, a general scheme of the receptor’s structure has been developed (3–8). Recently, our concept of the receptor’s structure has been refined by data obtained from cloning the receptor and other techniques (9–14). The picture that has emerged is that the predominant form of the receptor on the cell surface is that of a disulfide-linked heterotetrameric glycoprotein consisting of two distinct subunits, alpha and beta. Studies employing photoaffinity labeling techniques, as well as studies in which insulin is bound to and then affinity crosslinked to the receptor have shown that the alpha subunit contains the ligand binding region and hence must have a significant extracellular domain. In support of this, analysis of the sequence derived from the recent cloning of the receptor predicts that the alpha subunit lacks a significant hydrophobic region, suggesting that the alpha subunit is entirely extracellular. The beta subunit has a short extracellular domain, a hydrophobic membrane spanning region and an intracytoplasmic domain (13,14). As detailed below, this intracytoplasmic domain contains a tyrosine specific protein kinase activity (15–18). Upon binding of insulin to its receptor this kinase is somehow activated. Data are accumulating to suggest that activation of this kinase initiates a cascade of events leading to insulin’s bioeffects. Thus the alpha and beta subunits of the insulin receptor subserve distinct but interdependent functions in the pathway leading from insulin binding to insulin action.KeywordsInsulin ReceptorTyrosine Kinase ActivityWheat Germ AgglutininBeta SubunitInsulin BindingThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.