| Autor: |
Saltiel, Alan R., Pessin, Jeffrey E., De Meyts, Pierre, Sajid, Waseem, Palsgaard, Jane, Theede, Anne-Mette, Gauguin, Lisbeth, Aladdin, Hassan, Whittaker, Jonathan |
| Zdroj: |
Mechanisms of Insulin Action; 2007, p1-32, 32p |
| Abstrakt: |
The insulin and IGF-I receptors are members of the superfamily of receptor tyrosine kinases (RTKs). Unlike most RTKs that are single-chain monomeric transmembrane polypeptides, the insulin and IGF-I receptors are covalent dimers composed of two extracellular α subunits and two transmembrane β subunits containing the tyrosine kinase domains. The α subunits contain the ligand binding sites, of which at least three subdomains have been defined by photoaffinity crosslinking, alanine-scanning mutagenesis or minimized receptor constructs. All RTKs are dimeric or oligomeric in the ligand-activated form. The residues of insulin involved in receptor binding have been mapped by alanine-scanning mutagenesis. They form at least two major epitopes that partially overlap with the dimer- and hexamer-forming surfaces of the insulin molecule, and we propose that insulin is using those surfaces to asymmetrically cross-link the two receptor α subunits. This mechanism provides a structural basis for high affinity binding and negative cooperativity, and probably also operates in the IGF-receptor interaction. It also provides a structural basis for the approximation and transphosphorylation of the kinase domains and triggering of the signalling cascade. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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