Increased tyrosine kinase activity of c-Src during calcium-induced keratinocyte differentiation.

In cultured human epidermal keratinocytes, induction of differentiation by Ca2+ and ionophore treatment was found to result in rapid elevation of c-Src tyrosine kinase activity and inactivation of the c-Yes tyrosine kinase. Activation of c-Src kinase was accompanied by tyrosine dephosphorylation, which might be explained by a rapid increase in intracellular protein-tyrosine phosphatase activity. Ca(2+)-induced differentiation was also associated with altered tyrosine phosphorylation of several cellular proteins and correlated with a marked redistribution of intracellular phosphotyrosine from membrane and adhesion sites to the nucleus. Some of the c-Src protein was also found in the nucleus after Ca2+ treatment, and Ca(2+)-activated c-Src bound to three cellular proteins (120 kDa, 65 kDa, and 34 kDa). In agreement with these results, immunohistochemistry on human epidermis revealed an increase in c-Src expression and tyrosine phosphorylation in cells undergoing differentiation, which strongly suggests a possible role of non-receptor tyrosine kinases in epithelial cell maturation.