Reactome | Autophosphorylation of KIT

Autophosphorylation of KIT

Stable Identifier

R-HSA-205289

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

ReviewStatus

5/5

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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
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 Besmer, P, Serve, H, Hsu, YC	J Biol Chem	1994
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 Carlberg, M, Thömmes, K, Lennartsson, J, Rönnstrand, L	Biochem J	1999
9038210	Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes Price, DJ, Jiang, S, Avraham, H, Rivnay, B, Avraham, S, Fu, Y	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 Sridhar, V, Mol, CD, Lim, KB, McRee, DE, Chien, EY, Kassel, DB, Cronin, CN, Sang, BC, Nowakowski, J, Zou, H	J Biol Chem	2003