Activation of c-Src kinase is associated with in vitro decidualization of human endometrial stromal cells.
Tyrosine phosphorylation of cellular proteins, controlled coordinately by tyrosine kinases and phosphatases, is a critical element in signal transduction pathways involved in the regulation of biological responses including cell growth and differentiation. Decidualization is a dramatic progesterone-induced differentiation of the estrogen-primed endometrium, which is crucial for embryo implantation and maintenance of pregnancy. Here we have shown that the kinase activity of c-Src was increased, accompanied by altered tyrosine phosphorylation of several cellular proteins, during in vitro decidualization of human endometrial stromal cells. Withdrawal of both estrogen and progesterone from the cultures of decidualized stromal cells reduced c-Src kinase activity to the basal level and also changed the pattern of tyrosine phosphorylation of the several cellular proteins to the unstimulated state. The kinase activity of endometrial c-Src appeared to inversely correlate with the level of its tyrosine phosphorylation. Moreover, although the endometrial stromal cells expressed another src-family kinase, Fyn, the activity of the Fyn kinase was almost undetectable during decidualization and thereafter upon steroid withdrawal. Our findings suggest that the activation of c-Src kinase may be a normal physiological event associated with decidualization, being specifically involved in the signaling cascades mediated by ovarian hormone stimulation.
Maruyama
T
T
Department of Biological Responses, Institute for Virus Research, Kyoto University, Japan.
Yoshimura
Y
Y
Yodoi
J
J
Sabe
H
H
D000081247:CSK Tyrosine-Protein Kinase; D002478:Cells, Cultured; D003656:Decidua / Q000502:physiology*; D004717:Endometrium / Q000166:cytology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D010766:Phosphorylation; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D017154:Stromal Cells / Q000502:physiology; D019061:src-Family Kinases
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; C000631346:CSK protein, human