title: Signaling pathways controlling trophoblast cell differentiation: Src family protein tyrosine kinases in the rat.
abstract: 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 p60c-src, p62c-yes, and p53/56lyn were present in the Rcho-1 rat trophoblast cell line and in differentiated trophoblast cells isolated from the developing rat placenta. p60c-src and p62c-yes were active in proliferating and differentiating trophoblast cells. During proliferation, p62c-yes exhibited distinct associations with other phosphoproteins (34, 66, 76, and 150 kDa). p53/56lyn was activated only in differentiating trophoblast cells. p53/56lyn showed a differentiation-dependent accumulation in cytoskeletal and membrane fractions, whereas p60c-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 p53/56lyn; however, there was some indication of the participation of a tyrosine phosphatase in the regulation of p53/56lyn. In conclusion, p60c-src, p62c-yes, and p53/56lyn patterns of activation in trophoblast cells are consistent with their involvement in the control of trophoblast cell proliferation and differentiation.
authors.affiliation: Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City 66160, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kamei
authors.forename: G P
authors.initials: GP
authors.lastname: Hamlin
authors.forename: B M
authors.initials: BM
authors.lastname: Chapman
authors.forename: A L
authors.initials: AL
authors.lastname: Burkhardt
authors.forename: J B
authors.initials: JB
authors.lastname: Bolen
authors.forename: M J
authors.initials: MJ
authors.lastname: Soares
mesh_terms: D000818:Animals; D016227:Benzoquinones; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051575:Proto-Oncogene Proteins c-yes; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D014327:Trophoblasts / Q000166:cytology* / Q000201:enzymology*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D011518:Proto-Oncogene Proteins; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D051575:Proto-Oncogene Proteins c-yes; D016392:Proto-Oncogene Proteins pp60(c-src); C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases