FRS2 Products

Description

FGFs (Fibroblast Growth Factors) bind to FGF receptors (FGFRs) monovalently, and FGF receptor dimerization and activation is mediated by multivalent interactions between heparin sulfate proteoglycans and FGF. Upon activation, receptor tyrosine kinases undergo rapid autophosphorylation on numerous tyrosine residues. Autophosphorylation sites located within the catalytic domain are crucial for stimulation of kinase activity, while autophosphorylation sites located in other regions are usually involved in the recruitment of cellular target proteins. Fibroblast growth factor or nerve growth factor (NGF) stimulation leads to tyrosine phosphorylation of the FGF Receptor Substrate 2 (FRS2) docking proteins. FRS2 is also designated SNT (Suc-1 associated neurotrophic factor target protein). Two structurally similar forms of FRS2 are: FRS2a (SNT-1) and FRS-2b (SNT-2, FRS3). FRS functions as a lipid-anchored docking protein that is tyrosine phosphorylated and recruited to FGFR upon FGF stimulation. FRS2 plays an important role in linking FGF and NGF with the Ras/MAPK signaling pathway, thus relaying information from the cell surface to the nucleus. FRS2 contains both a consensus myristylation sequence, involved in its recruitment to the cell membrane and a putative phosphotyrosine binding (PTB)domain in its amino-terminus. The interaction of FRS2 with FGFR1 occurs via the PTB domain of FRS2 binding to a 12-residue segment in the juxtamembrane region of FGFR1. FRS2a contains four binding sites for the adaptor protein Grb2 and two binding sites for the protein tyrosine phosphatase Shp2. FGF stimulation leads to phosphorylation of Shp2 on a tyrosine residue forming a complex with an additional molecule of Grb2. Grb2/Sos complexes are thus recruited directly and indirectly via Shp2 upon tyrosine phosphorylation of FRS2a in response to growth factor stimulation. It has been shown that FRS2 proteins are tyrosine phos phorylated in response to activation of the RET receptor, a tyrosine kinase that functions as the signal transducing receptor for the GDNF.

Bioinformatics

Entrez	10818 Human
Uniprot	AAH21562 Human AAH21562.1 Human NM_006654 Human NP_001036020 Human NP_006645.3 Human
Product By Gene ID	10818
Alternate Names	FGFR signalling adaptor FGFR-signaling adaptor SNT fibroblast growth factor receptor substrate 2 FRS2A FRS2alpha SNT SNT1 SNT-1FGFR substrate 2 Suc1-associated neurotrophic factor target 1

Research Areas for FRS2

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Cancer
Signal Transduction