Reactome | Recruitment of CBL to KIT

Recruitment of CBL to KIT

Stable Identifier

R-HSA-205244

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region, cytosol

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

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
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
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
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, Yoshimura, A, Gottfridsson, E, Lennartsson, J, Rönnstrand, L	Biochem J	2003