The biological activity of the human epidermal growth factor receptor is positively regulated by its C-terminal tyrosines.

作者: Vass Wc , Lowy Dr , Helin K , Allevato G , Beguinot L

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摘要: The epidermal growth factor receptor (EGF-R) C-terminus contains three conserved tyrosines (Y-1068, Y-1148, Y-1173) which are phosphorylated upon EGF activation. To clarify the functional role of these tyrosines, each has been mutated to phenylalanine and studied as single, double triple mutants in full length receptor. EGF-dependent transforming ability single point is similar that wild type, while decreased an even lower activity present mutant. In bioassay, including focal transformation, agar low serum, mutant receptors display a hierarchy activity. intrinsic since they expressed at level type bind with affinity. Deletion lacking last 19 or 63 amino acids (Velu et al., 1989a) show decline biological when compared corresponding mutants, although reduction more pronounced than mutants. 123 aa, removes all (Dc123), results almost inactive biologically. EGF-R kinase affected by tyrosine substitution vitro phosphorylation exogenous substrates reduced Autophosphorylation, vivo vitro, also reduced, but not totally abolished Dc123 indicating existence other autophosphorylation sites. A new site found We conclude, therefore, extreme positively regulate EGF-R, probably via autophosphorylation.

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