Reactome | Activated ERK1/2 threonine-phosphorylates FGFR1-associated FRS2.

Activated ERK1/2 threonine-phosphorylates FGFR1-associated FRS2.

Stable Identifier

R-HSA-5654560

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, extracellular region, plasma membrane

ReviewStatus

5/5

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Activated ERK1/2 threonine-phosphorylates FGFR1-associated FRS2.

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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