Reactome | FRS-mediated FGFR1 signaling

FRS-mediated FGFR1 signaling

Stable Identifier

R-HSA-5654693

Type

Pathway

Species

Homo sapiens

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The FRS family of scaffolding adaptor proteins has two members, FRS2 (also known as FRS2 alpha) and FRS3 (also known as FRS2beta or SNT-2). Activation of FGFR tyrosine kinase allows FRS proteins to become phosphorylated on tyrosine residues and then bind to the adaptor GRB2 and the tyrosine phosphatase PPTN11/SHP2. Subsequently, PPTN11 activates the RAS-MAP kinase pathway and GRB2 activates the RAS-MAP kinase , PI-3-kinase and ubiquitinations/degradation pathways by binding to SOS, GAB1 and CBL, respectively, via the SH3 domains of GRB2. FRS2 acts as a central mediator in FGF signaling mainly because it induces sustained levels of activation of ERK with ubiquitous expression.

Literature References

PubMed ID	Title	Journal	Year
18452557	Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins Gotoh, N	Cancer Sci	2008
11447289	Critical role for the docking-protein FRS2 alpha in FGF receptor-mediated signal transduction pathways Hadari, YR, Gotoh, N, Kouhara, H, Lax, I, Schlessinger, J	Proc Natl Acad Sci U S A	2001
15863030	Cellular signaling by fibroblast growth factor receptors Eswarakumar, VP, Lax, I, Schlessinger, J	Cytokine Growth Factor Rev	2005
16682955	Expression of the SNT-1/FRS2 phosphotyrosine binding domain inhibits activation of MAP kinase and PI3-kinase pathways and antiestrogen resistant growth induced by FGF-1 in human breast carcinoma cells Manuvakhova, M, Thottassery, JV, Hays, S, Qu, Z, Rentz, SS, Westbrook, L, Kern, FG	Oncogene	2006