SIGNALING PATHWAYS CONTROLLING TROPHOBLAST CELL-DIFFERENTIATION - SRCFAMILY PROTEIN-TYROSINE KINASES IN THE RAT

Trophoblast giant cell differentiation is characterized by endoredupli cation and expression of members of the prolactin (PRL) gene family an d can be simulated in vitro via manipulations of the Rcho-1 trophoblas t cell line. The regulation of trophoblast cell proliferation and diff erentiation involves tyrosine protein kinase signaling pathways. Treat ment of Rcho-1 trophoblast cells with tyrosine kinase inhibitors disru pted differentiation-dependent expression of members of the PRL gene f amily and cytoskeletal organization. Activated p60(c-src), p62(c-yes), and p53/56(lyn) were present in the Rcho-1 rat trophoblast cell line and in differentiated trophoblast cells isolated from the developing r at placenta. p60(c-src) and p62(c-yes) were active in proliferating an d differentiating trophoblast cells. During proliferation, p62(c-yes) exhibited distinct associations with other phosphoproteins (34, 66, 76 , and 150 kDa). p53/56(lyn) was activated only in differentiating trop hoblast cells. p53/56(lyn) showed a differentiation-dependent accumula tion in cytoskeletal and membrane fractions, whereas p60(c-src) levels were virtually invariant in both fractions. Expression patterns of cs k, a negative regulator of Src family kinase activities, were not cons istent with its involvement in the differentiation-dependent activatio n of p53/56(lyn); however, there was some indication of the participat ion of a tyrosine phosphatase in the regulation of p53/56(lyn). In con clusion; p60(c-src), p62(c-yes), and p53/56(lyn) patterns of activatio n in trophoblast cells are consistent with their involvement in the co ntrol of trophoblast cell proliferation and differentiation.