Activation of c-Src kinase is associated with in vitro decidualization of human endometrial stromal cells

Tyrosine phosphorylation of cellular proteins, controlled coordinately by t yrosine kinases and phosphatases, is a critical element in signal transduct ion pathways involved in the regulation of biological responses including c ell growth and differentiation. Decidualization is a dramatic progesterone- induced differentiation of the estrogen-primed endometrium, which is crucia l for embryo implantation and maintenance of pregnancy. Here we have shown that the kinase activity of c-Src was increased, accompanied by altered tyr osine phosphorylation of several cellular proteins, during in vitro decidua lization of human endometrial stromal cells. Withdrawal of both estrogen an d progesterone from the cultures of decidualized stromal cells reduced c-Sr c kinase activity to the basal level and also changed the pattern of tyrosi ne phosphorylation of the several cellular proteins to the unstimulated sta le. The kinase activity of endometrial c-Src appeared to inversely correlat e with the level of its tyrosine phosphorylation. Moreover, although the en dometrial stromal cells expressed another src-family kinase, Fyn, the activ ity of the Fyn kinase was almost undetectable during decidualization and th ereafter upon steroid withdrawal. Our findings suggest that the activation of c-Src kinase may be a normal physiological event associated with decidua lization, being specifically involved in the signaling cascades mediated by ovarian hormone stimulation.