Multiple autophosphorylation sites of the epidermal growth factor receptor are essential for receptor kinase activity and internalization. Contrasting significance of tyrosine 992 in the native and truncated receptors.

摘要: The role of epidermal growth factor (EGF) receptor autophosphorylation sites in the regulation functions has been studied using cells transfected with mutant EGF receptors. Simultaneous point mutation 4 tyrosines (Y1068, Y1086, Y1148, Y1173) to phenylalanine, as well removal these by truncation carboxyl-terminal 123 amino acid residues, resulted reduced phosphorylation an vivo specific substrate phospholipase C-gamma 1 less than 50% compared wild-type receptor. internalization rate constant Ke was also significantly lower mutants (0.15/min) (0.27/min). Additional tyrosine 992 phenylalanine truncated (Dc-123F) further decreased a minimal level (ke = 0.07-0.10/min), equivalent ke measured for expressing kinase-negative (A721). Moreover, kinase activity Dc-123F toward 1, receptor, 90%. Taken together, results show that lacking five similar Mutation residue Y992 alone context full length however, did not affect or 1. These data indicate is critical and only minor sites, such Y992, may act compensatory regulatory sties absence major sites.