Reactome | CBL ubiquitinates FRS2 and FGFR2

CBL ubiquitinates FRS2 and FGFR2

Stable Identifier

R-HSA-5654677

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

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

Grb2 bound to tyrosine phosphorylated FRS2 forms a ternary complex with Cbl through the binding of the SH3 domains of Grb2 to a proline rich region in Cbl. Grb2-mediated recruitment of Cbl results in ubiquitination of FGFR and FRS2. Cbl is a multidomain protein that posses an intrinsic ubiquitin ligase activity and also functions as a platform for recruitment of a variety of signaling proteins. Multiple mechanisms appear to be required for downregulation of FGFR, as internalization of the receptor is reduced but not abolished if recruitment of CBL to FRS2 is compromised by mutation of GRB2-binding sites.

Literature References

PubMed ID	Title	Journal	Year
12815057	Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is crucial for its function Fong, CW, Leong, HF, Wong, ES, Lim, J, Yusoff, P, Guy, GR	J Biol Chem	2003
11997436	FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl Wong, A, Lamothe, B, Lee, A, Schlessinger, J, Lax, I	Proc Natl Acad Sci U S A	2002