Reactome | Negative regulation of FGFR4 signaling

Negative regulation of FGFR4 signaling

Stable Identifier

R-HSA-5654733

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, extracellular region, plasma membrane

ReviewStatus

5/5

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Once activated, the FGFR signaling pathway is regulated by numerous negative feedback mechanisms. These include downregulation of receptors through CBL-mediated ubiquitination and endocytosis, ERK-mediated inhibition of FRS2-tyrosine phosphorylation and the attenuation of ERK signaling through the action of dual-specificity phosphatases, IL17RD/SEF, Sprouty and Spred proteins. A number of these inhibitors are themselves transcriptional targets of the activated FGFR pathway.

Literature References

PubMed ID	Title	Journal	Year
20940169	Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease Itoh, N, Ornitz, DM	J Biochem	2011
12815057	Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is crucial for its function Yusoff, P, Fong, CW, Wong, ES, Lim, J, Leong, HF, Guy, GR	J Biol Chem	2003
11997436	FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl Wong, A, Lee, A, Lamothe, B, Schlessinger, J, Lax, I	Proc Natl Acad Sci U S A	2002
18452557	Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins Gotoh, N	Cancer Sci	2008