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

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Activated ERK1/2 threonine-phosphorylates FGFR1-associated FRS2

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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