Activated ERK1/2 threonine-phosphorylates FGFR4-associated FRS2.

Stable Identifier
Reaction [transition]
Homo sapiens
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FRS2 has 8 canonical MAPK phosphorylation sites which are phosphorylated by activated ERK1/2 after FGF stimulation. Phosphorylation of these 8 threonine residues counteracts the activating effect of tyrosine phosphorylation of FRS2, although the exact mechanism for this negative regulation is not known. Expression of a version of FRS2 in which the 8 threonine residues are mutated to valine results in enhanced tyrosine phosphorylation of FRS2, enhanced GRB2-SOS1 recruitment and a more sustained MAPK response. The 8 threonine residues are not conserved in FRS3; as a result, signaling through FRS3 complexes do not appear to be subject to this downregulation.
Literature References
PubMed ID Title Journal Year
12419216 The docking protein FRS2alpha controls a MAP kinase-mediated negative feedback mechanism for signaling by FGF receptors

Frost, A, Wong, A, Hawes, J, Lee, A, Lamothe, B, Schlessinger, J, Lax, I

Mol Cell 2002
12974390 EGFR and FGFR signaling through FRS2 is subject to negative feedback control by ERK1/2

Chen, Z, Ullrich, A, Wu, Y

Biol Chem 2003
19652666 FGF-receptor substrate 2 functions as a molecular sensor integrating external regulatory signals into the FGF pathway

Chen, Z, Zhou, W, Zhang, Z, Benge, J, Feng, X, Wu, Y

Cell Res 2009
18452557 Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins

Gotoh, N

Cancer Sci 2008
Catalyst Activity

MAP kinase activity of p-T,Y MAPK dimers [cytosol]

Orthologous Events
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