Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation.

摘要: The membrane receptor for epidermal growth factor (EGF) is a 170,000-dalton glycoprotein composed of an extracellular EGF-binding domain and cytoplasmic kinase connected by stretch 23 amino acids traversing the plasma membrane. binding EGF to activates function even in highly purified preparations receptor, suggesting that activation occurs exclusively within moiety. Conceivably, may require transfer conformational change through single transmembrane region from ligand region. Alternatively, ligand-induced receptor-receptor interactions activate thus bypass this requirement. Both mechanisms were contrasted employing independent experimental approaches. following lines evidence support intermolecular mechanism detergent-solubilized receptor: EGF-induced self-phosphorylation has parabolic dependence on concentration cross-linking receptors antibodies or lectins stimulates self-phosphorylation, immobilization various solid matrices prevents activating function, increases their affinity toward EGF. On basis these results, allosteric aggregation model formulated This be relevant which mitogenic signal transferred across