Reactome | Ubiquitination of stimulated EGFR (CBL)

Ubiquitination of stimulated EGFR (CBL)

Stable Identifier

R-HSA-182993

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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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