Ubiquitination of stimulated EGFR (CBL:GRB2)

Stable Identifier
Reaction [transition]
Homo sapiens
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CBL down-regulates receptor tyrosine kinases by conjugating ubiquitin to them. This leads to receptor internalization and degradation. The ubiquitin protein ligase activity of CBL (abbreviated as E3 activity) is mediated by its RING finger domain. Receptor-type tyrosine-protein phosphatase kappa (PTPRK/RPTPk/DEP1) dephosphorylates EGFR, thereby inhibiting receptor ubiquitylation (Ub) by c-CBL, which decelerates the rate of receptor internalization and diminishes MAPK signals generated at the membrane and in endosomes. PTPRK disrupts physical association of ubiquitin ligase complex with EGFR and impairs its internalization (Tarcic et al. 2009, Xu et al. 2005).

Literature References
PubMed ID Title Journal Year
15021893 Role of protein ubiquitylation in regulating endocytosis of receptor tyrosine kinases

Marmor, MD, Yarden, Y

Oncogene 2004
10514377 The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase

Huang, H, Liu, YC, Hunter, T, Leverson, JD, Wing, SS, Joazeiro, CA

Science 1999
Catalyst Activity

ubiquitin protein ligase activity of EGF-like ligands:p-6Y-EGFR:p-Y371-CBL:GRB2 [plasma membrane]

This event is regulated
Negatively by