Signalling through the insulin receptor and the insulin-like growth factor-I receptor.
The insulin receptor and the insulin-like growth factor I receptor belong to the family of tyrosine kinase receptors. Both receptors appear as a disulphide-linked dimer; each half of the dimer consisting of a 130 k M(r) alpha-subunit linked to a 90 k M(r) beta-subunit. Both halves of the dimer are linked together by disulphide bonds to form an alpha 2 beta 2 structure. The insulin receptor functions as an allosteric enzyme in which the binding of the hormone to the alpha-subunit leads to a series of conformational changes resulting in activation of the beta-subunit tyrosine kinase. Upon multisite autophosphorylation the latter becomes competent to phosphorylate cellular substrates resulting in the biological responses of insulin. Recent findings have recognized the mitogen activated protein kinase cascade as a central signalling circuitry linking cell surface receptors, such as the insulin receptor, to the nucleus, and playing a role in regulation of metabolism, growth and differentiation.
Van Obberghen
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INSERM U 145, Faculté de Médecine, Nice, France.
D000595:Amino Acid Sequence; D000818:Animals; D001363:Awards and Prizes; D001530:Belgium; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D016384:Consensus Sequence; D003920:Diabetes Mellitus / Q000266:history; D005060:Europe; D049673:History, 20th Century; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1 / Q000737:chemistry / Q000502:physiology*; D011972:Receptor, Insulin / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D012955:Societies, Medical
D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases