Alteration of epidermal growth factor receptor activity by mutation of its primary carboxyl-terminal site of tyrosine self-phosphorylation.

摘要: Abstract The epidermal growth factor (EGF) receptor, which exhibits intrinsic protein tyrosine kinase activity, undergoes a rapid, intramolecular self-phosphorylation reaction following EGF activation. primary sites of in vivo are located the extreme carboxyl-terminal region molecule, principally Tyr-1173. To test biological and biochemical consequences this receptor self-phosphorylation, we made mutation Tyr----Phe-1173. Membranes containing mutated exhibited an ED50 for activation activity equivalent to control at both high low substrate levels, but reduced basal EGF-stimulated low, non-saturating levels. Tyr----Phe-1173 mutant possessed affinity binding could still self-phosphorylate other fashion with Km ATP (200 nM), suggesting that alteration did not grossly change structure. When EGF-dependent Chinese hamster ovary cells expressing comparable levels or was measured, ability mediate cell response by approximately 50%, yet receptors similar EGF. These results support concept site can act as competitive/alternate molecule is important modulating its maximal activity.