p-KIT complex Autophosphorylation of KIT Authored: Garapati, P V, 2011-07-11 EC Number: 2.7.10 Edited: Garapati, P V, 2011-07-11 Pubmed10377264 Pubmed12824176 Pubmed16129412 Pubmed20147452 Pubmed7509796 Pubmed9038210 Reactome Database ID Release 43205289 Reactome, http://www.reactome.org ReactomeREACT_111103 Reviewed: Rönnstrand, L, 2011-08-22 The cytoplasmic domain of KIT contains a bipartite kinase domain separated by 77 residues. The first part of the catalytic domain contains the ATP binding region while the second part contains an activation loop. Both parts of the domain have a number of possible autophosphorylation sites. In contrast to many other tyrosine kinases, autophosphorylation of the activation loop does not seem to be involved in the activation of the kinase activity nor it is required for full kinase activity (DiNitto et al. 2010). Instead, phosphorylation sites in the juxtamembrane region are important for activation of the kinase activity. The dimerized KIT acts as both enzyme and substrate for itself and autophosphorylates these specific tyrosine residues with in the kinases domains in trans as well as tyrosine residues outside the kinase domain. The resulting phosphotyrosine residues serve as docking sites for a number of signal transduction molecules containing Src-homology 2 (SH2) and phosphotyrosine-binding (PTB) domains. A majority of the autophosphorylation sites reside outside the kinase domain. has a Stoichiometric coefficient of 14 KIT:sSCF dimer:KIT