FRS-mediated FGFR3 signaling

Stable Identifier
R-HSA-5654706
Type
Pathway
Species
Homo sapiens
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Summation

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
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