tooltip layer (initially hidden)
signaling gateway home
Protein A000967
Author-entered Data
V1.0, Peer Reviewed
Published 7 May 2009
Automated Data
Not Reviewed
As At Publication
Automated Data
Not Reviewed
Latest from 6 Jun 2014

UCSD Nature Molecule Pages
Published online: 7 May 2009 | doi:10.1038/mp.a000967.01

Frs2 alpha

Basis Sequence: Mouse

Takuya Sato1, Noriko Gotoh1

1Division of Systems Biomedical Technology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, JP.

Correspondence should be addressed to Noriko Gotoh:

Fibroblast growth factor receptor substrate 2α (FRS2α) is a member of the FRS2 family of docking/scaffolding adaptor proteins. FRS2α contains amino (N)-terminal myristylation sequences and is constitutively anchored to the plasma membrane. It acts as a docking protein downstream of several receptor tyrosine kinases (RTKs), including fibroblast growth factor (FGF) receptors, neurotrophin receptors, ephrin receptor A4 (EphA4), RET, and anaplastic lymphoma kinase (ALK). FRS2α binds to these RTKs via its phosphotyrosine binding (PTB) domain and is tyrosine phosphorylated following RTK activation. FRS2α is perhaps best known for its function as a control center for intracellular signaling in response to FGF. Activation of FGFRs elicits tyrosine phosphorylation of FRS2α, which creates binding sites for Grb2 and Shp2. The FRS2α-Shp2 complex induces the tyrosine phosphorylation of Shp2, stimulating sustained activation of extracellular signal-regulated kinases (ERKs). Some proteins, namely SOS, Cbl, and Gab1, are constitutively bound via the two Src homology 3 (SH3) domains in Grb2. The ternary FRS2α-Grb2-SOS complex induces modest activation of the Ras/ERK pathway, whereas the FRS2α-Grb2-Cbl complex causes the ubiquitination and degradation of FRS2α and its receptors, and the FRS2α-Grb2-Gab1 complex induces the recruitment of PI-3 kinase and activation of Akt. Thus, FRS2α is required for various biological activities stimulated by FGF, including the proliferation and migration of cells, outgrowth of neurites and development of various organs and tissues. FRS2α-mutant mice exhibit various developmental defects, including those in anterior-posterior axis formation and the development of the extraembryonic ectoderm, cerebral cortex, eye, carotid body, cardiac outflow tract, prostate, limbs and skeleton. Many of these defects arise as a result of defects in FGF signaling during embryogenesis. FRS2α is also important for the maintenance and/or proliferation of several tissue-type-specific stem cells, including trophoblast stem cells and neural stem/progenitor cells.

Alternative names for this molecule: Fibroblast growth factor receptor substrate 2; FRS-2; Frs2; Frs2 alpha; FRS2A; FRS2alpha; SNT; SNT-1; SNT1; Suc 1-associated neurotrophic factor target (SNT-1); suc1-associated neurotrophic factor target (FGFR signalling adaptor)

Transition Network Graph This molecule exists in 40 states and has 42 transitions between these states.

[map] View high resolution network map

Acknowledgments: We thank Dr. J. Schlessinger for all the supports of our work in his laboratory.Work in our laboratory was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Ministry of Health, Labor and Welfare of Japan for the 3rd-term Comprehensive 10-year Strategy for Cancer Control and for Cancer Research, the Naito Foundation and the Cell Science Research Foundation.