Signaling pathways controlling trophoblast cell differentiation: Src family protein tyrosine kinases in the rat

Trophoblast giant cell differentiation is characterized by endoreduplication and expression of members of the prolactin (PRL) gene family and can be simulated in vitro via manipulations of the Rcho-1 trophoblast cell line. The regulation of trophoblast cell proliferation and differentiation involves tyrosine protein kinase signaling pathways. Treatment of Rcho-1 trophoblast cells with tyrosine kinase inhibitors disrupted differentiation-dependent expression of members of the PRL gene family 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 rat placenta. p60(c-src) and p62(c-yes) were active in proliferating and 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 trophoblast cells. p53/56(lyn) showed a differentiation-dependent accumulation in cytoskeletal and membrane fractions, whereas p60(c-src) levels were virtually invariant in both fractions. Expression patterns of csk, a negative regulator of Src family kinase activities, were not consistent with its involvement in the differentiation-dependent activation of p53/56(lyn); however, there was some indication of the participation of a tyrosine phosphatase in the regulation of p53/56(lyn). In conclusion, p60(c-src), p62(c-yes), and p53/56(lyn) patterns of activation in trophoblast cells are consistent with their involvement in the control of trophoblast cell proliferation and differentiation.