CBL ubiquitinates FRS2 and FGFR2

Stable Identifier
Reaction [transition]
Homo sapiens
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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

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
Catalyst Activity

ubiquitin protein ligase activity of Activated FGFR2:p-FRS2:p-PTPN11:p-CBL:GRB2 [plasma membrane]

Orthologous Events
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