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Protein A004122
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.a004122.01

Frs2 beta

Basis Sequence: Mouse

Yuriko Minegishi1, 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: ngotoh@ims.u-tokyo.ac.jp


Fibroblast growth factor receptor substrate 2β (FRS2β) is a member of the FRS2 family of docking/scaffolding adaptor proteins. An amino (N)-terminal myristoylation sequence directs FRS2β membrane localization. At the membrane, FRS2β interacts with several receptor tyrosine kinases (RTKs) and functions as a docking protein. FRS2β can interact with fibroblast growth factor (FGF) receptors and anaplastic lymphoma kinases (ALKs) in a phopsphorylation-independent manner, whereas the interaction between FRS2β and neurotrophin receptors (Trks) is dependent on receptor tyrosine phosphorylation. Ligand-bound and active RTKs phosphorylate the tyrosine residues of FRS2β, creating binding sites for the adaptor protein Grb2 and the SH2 domain-containing tyrosine phosphatase Shp2. The FRS2β-Shp2 complex activates the tyrosine phosphorylation of Shp2, resulting in strong activation of extracellular signal-regulated kinase (ERK) in response to FGF. Grb2-SOS complex recruitment via FRS2β is believed to activate the Ras/ERK pathway at moderate levels. In response to FGF, activated FRS2β stimulates neurite outgrowth in neuronal cells such as PC12 cells. By contrast, FRS2β is not phosphorylated on tyrosine residues by epidermal growth factor (EGF) stimulation; instead, it inhibits the tyrosine-kinase activity of EGFR, resulting in the suppression of EGF-induced cell proliferation and transformation. The binding between FRS2β and ERK is important for the inhibition of EGFR. Therefore, FRS2β is a unique scaffolding adaptor protein that serves as an interactive mediator that can both positively and negatively regulate RTK signaling by its specificity to RTKs. FRS2β expression is restricted in several tissues including neural tissues. Detailed information about the functions of FRS2β and phenotypes of the mutant mice is scarce; therefore, further investigation of this protein is required.

Alternative names for this molecule: FGFR substrate 3; FGFR-signaling adaptor SNT2; Fibroblast growth factor receptor substrate 3; Frs2 beta; FRS2-beta; Frs2b; FRS2B; Frs2beta; FRS2beta; Frs3; FRS3; SNT-2; Snt2; SNT2; Suc1-associated neurotrophic factor target 2; Suc1-associated neurotrophic factor target 2 (FGFR signalling adaptor)

Transition Network Graph This molecule exists in 25 states and has 28 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.