Autophosphorylation of KIT

Stable Identifier
R-HSA-205289
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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.

Literature References
PubMed ID Title Journal Year
10377264 Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor

Thömmes, K, Lennartsson, J, Carlberg, M, Rönnstrand, L

Biochem J 1999
7509796 Tyrosine residue 719 of the c-kit receptor is essential for binding of the P85 subunit of phosphatidylinositol (PI) 3-kinase and for c-kit-associated PI 3-kinase activity in COS-1 cells

Serve, H, Hsu, YC, Besmer, P

J Biol Chem 1994
9038210 Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes

Price, DJ, Rivnay, B, Fu, Y, Jiang, S, Avraham, S, Avraham, H

J Biol Chem 1997
16129412 Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor

Roskoski, R Jr

Biochem Biophys Res Commun 2005
12824176 Structure of a c-kit product complex reveals the basis for kinase transactivation

Mol, CD, Lim, KB, Sridhar, V, Zou, H, Chien, EY, Sang, BC, Nowakowski, J, Kassel, DB, Cronin, CN, McRee, DE

J Biol Chem 2003
Participants
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Catalyst Activity
Title
protein tyrosine kinase activity of KIT:sSCF dimer:KIT [plasma membrane]
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