Signaling pathways controlling trophoblast cell differentiation: Src family protein tyrosine kinases in the rat
Signaling pathways controlling trophoblast cell differentiation: Src family protein tyrosine kinases in the rat
复制标题
DOI：
10.1095/biolreprod57.6.1302
复制
发表时间：
1997-12-01
影响因子：
3.6
通讯作者：
Soares, MJ
中科院分区：
文献类型：
--
作者：
Kamei, T;Hamlin, GP;Soares, MJ
滋养层巨细胞分化的特征是催乳素(PRL)基因家族成员的内复制和表达，体外可以通过操纵Rcho-1滋养层细胞系来模拟。滋养层细胞增殖分化的调控涉及酪氨酸蛋白激酶信号转导通路。用酪氨酸激酶抑制剂处理Rcho-1滋养层细胞会破坏PRL基因家族成员的分化依赖性表达和细胞骨架组织。活化的p60(c-src)、p62(c-yes)和p53/56(Lyn)存在于Rcho-1大鼠滋养层细胞系和从发育中的大鼠胎盘分离的分化滋养层细胞中。P60(c-src)和p62(c-yes)对滋养层细胞的增殖和分化具有活性。在增殖过程中，p62(c-yes)与其他磷酸蛋白(34、66、76和150 kDa)显示出明显的相关性。P53/56(Lyn)仅在滋养层细胞分化时被激活。P53/56(Lyn)在细胞骨架和膜组分中呈分化依赖性蓄积，而p60(c-src)水平在这两个组分中几乎不变。作为Src家族激酶活性的负调控因子，CSK的表达模式与其参与P53/56(Lyn)的分化依赖性激活并不一致；然而，有迹象表明酪氨酸磷酸酶参与了P53/56(Lyn)的调节。结论：滋养层细胞中p60(c-src)、p62(c-yes)和p53/56(Lyn)的激活模式与它们参与调控滋养层细胞的增殖和分化是一致的。
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.