Recruitment of CBL to KIT Authored: Garapati, P V, 2011-07-11 Edited: Garapati, P V, 2011-07-11 Pubmed11994499 Pubmed12444928 Pubmed16780420 Pubmed17904548 Reactome Database ID Release 43205244 Reactome, http://www.reactome.org ReactomeREACT_111179 Reviewed: Rönnstrand, L, 2011-08-22 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) CBL:Grb2/p-APS:p-c-Kit complex Grb2:SOS:p-c-Kit/p-APS:p-c-Kit complex