کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2177848 1094679 2006 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
An Shp2/SFK/Ras/Erk Signaling Pathway Controls Trophoblast Stem Cell Survival
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
An Shp2/SFK/Ras/Erk Signaling Pathway Controls Trophoblast Stem Cell Survival
چکیده انگلیسی

SummaryLittle is known about how growth factors control tissue stem cell survival and proliferation. We analyzed mice with a null mutation of Shp2 (Ptpn11), a key component of receptor tyrosine kinase signaling. Null embryos die peri-implantation, much earlier than mice that express an Shp2 truncation. Shp2 null blastocysts initially develop normally, but they subsequently exhibit inner cell mass death, diminished numbers of trophoblast giant cells, and failure to yield trophoblast stem (TS) cell lines. Molecular markers reveal that the trophoblast lineage, which requires fibroblast growth factor-4 (FGF4), is specified but fails to expand normally. Moreover, deletion of Shp2 in TS cells causes rapid apoptosis. We show that Shp2 is required for FGF4-evoked activation of the Src/Ras/Erk pathway that culminates in phosphorylation and destabilization of the proapoptotic protein Bim. Bim depletion substantially blocks apoptosis and significantly restores Shp2 null TS cell proliferation, thereby establishing a key mechanism by which FGF4 controls stem cell survival.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 10, Issue 3, March 2006, Pages 317–327
نویسندگان
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