Protein tyrosine phosphorylation signaling in the differentiation of human endometrial stromal cells.
Reversible protein tyrosine phosphorylation, coordinately controlled by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), is a critical element in signal transduction pathways regulating cell growth, differentiation, apoptosis, and tumorigenesis. The differentiation of human endometrial stromal cells (decidualization) is crucial for successful embryo implantation and maintenance of pregnancy; however, little is known about the molecular events involving tyrosine phosphorylation, PTKs, and PTPs in the process of decidualization. We have previously reported that the tyrosine kinase activity of c-Src belonging to the Src family kinase is increased together with altered tyrosine phosphorylation of several cellular proteins in the in vitro model of decidualization. Focal adhesion kinase (FAK) and paxillin are known to form a complex with c-Src at the focal contacts and to participate in the integrin-mediated signal transduction as c-Src substrates. Those focal adhesion proteins, however, are not hyperphosphorylated on tyrosine during decidualization. Moreover, the loss of focal adhesions and the disorganization of the actin-based cytoskeleton were observed in decidualized stromal cells, suggesting that the escape from regulation by c-Src may be in part due to the decidualization-induced disruption of the interaction between the focal adhesion proteins and c-Src. These findings collectively indicate that decidual c-Src may activate signaling pathway(s) different from the integrin-mediated signaling cascade involving FAK and paxillin. This review summarizes our recent studies on the tyrosine phosphorylation signaling pathway(s) in decidualization.
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan. tetsuo@sc.itc.keio.ac.jp
Tetsuo
T
Maruyama
Yurie
Y
Yamamoto
Nozomi
N
Sakai
Aki
A
Shimizu
Asuka
A
Shimoki
Takahiro
T
Masuda
Yasunori
Y
Yoshimura
D002454:Cell Differentiation / Q000502:physiology; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D014443:Tyrosine