Kinetic model of the epidermal growth factor (EGF) receptor tyrosine kinase and a possible mechanism of its activation by EGF.

摘要: The tyrosine kinase activity of the epidermal growth factor receptor (EGFR-TK) was determined at varying poly-Glu6Ala3Tyr1 (GAT) or [Val5]-angiotensin II (AT) and constant ATP concentrations vice versa. With GAT as substrate, double reciprocal plots intersected practically on abscissa following EGFR-TK pre-activation with EGF, but below without EGF pre-activation. inhibitors App(NH)p (5'-adenylyl-beta, gamma-imidodiphosphate) ADP were competitive noncompetitive GAT. Four families 1/v vs. 1/[ATP] plots, constructed different fixed a concentration for each family, yielded Slope1/ATP replots which to left ordinate abscissa. AT, cosubstrates, other ATP; 1/[GAT] 1/[AT] hyperbolic reached horizontal asymptotes when v expressed rate common product formation. All data subjected computer best-fit analysis by program written especially this purpose. We conclude that (i) reaction follows Sequential Bi-Bi Rapid Equilibrium Random mechanism, (ii) induces conformational changes in active center lead marked decreases apparent dissociation constants both substrates concomitant increase initial velocities Vmax (apparent).