Tyrosine phosphorylation of p60c-src induced by Zn2+ in rat hippocampal membranes is shown to inhibit Src tyrosine kinase activity, Zn2+ catalyzes the phosphorylation of p60c-scr in the membranes but does not activate autophosphorylation of p60c-scr immunoprecipitated with anti-Scr monoclonal antibody. Moreover, the immunoprecipitated Src kinase has no Zn2+-induced activity in phosphorylation of exogenous substrate, enolase. Cyanogen bromide cleavage of p60c-src phosphorylated in the presence of Zn2+ yields a 4-kDa phosphopeptide corresponding to phosphorylation of a carboxy-terminal tyrosine residue of Src kinase. In conclusion, hippocampal membranes contain a Zn2+-stimulated protein tyrosine kinase capable of regulating the p60c-src activity.
