{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:58:17Z","timestamp":1778687897004,"version":"3.51.4"},"reference-count":23,"publisher":"Proceedings of the National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,7,17]]},"abstract":"<jats:p>The docking protein FRS2\u03b1 has been implicated as a mediator of signaling via fibroblast growth factor receptors (FGFRs). We have demonstrated that targeted disruption of FRS2\u03b1 gene causes severe impairment in mouse development resulting in embryonal lethality at E7.0\u2013E7.5. Experiments with FRS2\u03b1-deficient fibroblasts demonstrate that FRS2\u03b1 plays a critical role in FGF-induced mitogen-activated protein (MAP) kinase stimulation, phosphatidylinositol-3 (PI-3) kinase activation, chemotactic response, and cell proliferation. Following FGF stimulation, tyrosine phosphorylated FRS2\u03b1 functions as a site for coordinated assembly of a multiprotein complex that includes Gab1 and the effector proteins that are recruited by this docking protein. Furthermore, we demonstrate that different tyrosine phosphorylation sites on FRS2\u03b1 are responsible for mediating different FGF-induced biological responses. These experiments establish the central role of FRS2\u03b1 in signaling via FGFRs and demonstrate that FRS2\u03b1 mediates multiple FGFR-dependent signaling pathways critical for embryonic development.<\/jats:p>","DOI":"10.1073\/pnas.161259898","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:34:10Z","timestamp":1027694050000},"page":"8578-8583","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":261,"title":["Critical role for the docking-protein FRS2\u03b1 in FGF receptor-mediated signal transduction pathways"],"prefix":"10.1073","volume":"98","author":[{"given":"Y. 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