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Critical role for the docking-protein FRS2[Alpha] in FGF receptor-mediated signal transduction pathways

Authors :
Hadari, Y. R.
Gotoh, N.
Kouhara, H.
Lax, I.
Schlessinger, J.
Source :
Proceedings of the National Academy of Sciences of the United States. July 17, 2001, Vol. 98 Issue 15, 8578
Publication Year :
2001

Abstract

The docking protein FRS2[Alpha] has been implicated as a mediator of signaling via fibroblast growth factor receptors (FGFRs). We have demonstrated that targeted disruption of FRS2[Alpha] gene causes severe impairment in mouse development resulting in embryonal lethality at E7.0-E7.5. Experiments with FRS2[Alpha]-deficient fibroblasts demonstrate that FRS2[Alpha] plays a critical role in FGF-induced mitogen-activated protein (MAP) kinase stimulation, phosphatidylinositol-3 (Pl-3) kinase activation, chemotactic response, and cell proliferation. Following FGF stimulation, tyrosine phosphorylated FRS2[Alpha] 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[Alpha] are responsible for mediating different FGF-induced biological responses. These experiments establish the central role of FRS2[Alpha] in signaling via FGFRs and demonstrate that FRS2[Alpha] mediates multiple FGFR-dependent signaling pathways critical for embryonic development.

Details

ISSN :
00278424
Volume :
98
Issue :
15
Database :
Gale General OneFile
Journal :
Proceedings of the National Academy of Sciences of the United States
Publication Type :
Academic Journal
Accession number :
edsgcl.77280080