Recruitment of CBL to KIT

Stable Identifier
R-HSA-205244
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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The phosphotyrosine residue in APS creates a putative binding site for CBL. CBL is an ubiquitin E3 ligase that attaches ubiquitin to KIT leading to KIT's ubiquitination followed by internalization and degradation. GRB2 in addition to its role in positive signaling via RAS/ERK pathway also mediates negative regulation of KIT by recruiting CBL (Sun et al, 2007). CBL has also been shown to bind directly to both Y568 and Y936 in KIT (Masson et al. 2006). CBL bound to KIT ubiquitinates KIT and targets it to lysosomal degradation (Masson et al. 2006)

Literature References
PubMed ID Title Journal Year
11994499 The Cbl family of ubiquitin ligases: critical negative regulators of tyrosine kinase signaling in the immune system

Rao, N, Dodge, I, Band, H

J Leukoc Biol 2002
17904548 Grb2 mediates negative regulation of stem cell factor receptor/c-Kit signaling by recruitment of Cbl

Sun, J, Pedersen, M, Bengtsson, S, Rönnstrand, L

Exp Cell Res 2007
16780420 Direct binding of Cbl to Tyr568 and Tyr936 of the stem cell factor receptor/c-Kit is required for ligand-induced ubiquitination, internalization and degradation

Masson, K, Heiss, E, Band, H, Rönnstrand, L

Biochem J 2006
12444928 The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit

Wollberg, P, Lennartsson, J, Gottfridsson, E, Yoshimura, A, Rönnstrand, L

Biochem J 2003
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