Signaling by juxtamembrane domain KIT mutants

Stable Identifier
Homo sapiens
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Mutations in the juxtamembrane region of KIT, encoded by exon 11, are especially prevalent as initiating events in gastrointestinal stromal tumors (GIST), but are also found at lower frequency in other cancers such as AML and melanoma (reviewed in Antonescu, 2006; Roskoski, 2018). Mutations in this region of KIT are believed to disrupt an auto-inhibitory function, leading to constitutive enzyme activation (Ma et al, 1999; Chan et al, 2003; Mol et al, 2004; reviewed in Roskoski, 2018). Unlike kinase domain mutants, juxtamembrane domain KIT mutants still undergo dimerization, although in a ligand-independent manner (Hirota et al, 1998; Furitsu et al, 1993; reviewed in Lennartsson and Roonstrand, 2012).
Literature References
PubMed ID Title Journal Year
12697809 Autoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane region

Rottapel, R, Ilangumaran, S, Chakrabartty, A, Chan, PM, La Rose, J

Mol. Cell. Biol. 2003
23073628 Stem cell factor receptor/c-Kit: from basic science to clinical implications

Rönnstrand, L, Lennartsson, J

Physiol. Rev. 2012
17193819 Gastrointestinal stromal tumor (GIST) pathogenesis, familial GIST, and animal models

Antonescu, CR

Semin Diagn Pathol 2006
15123710 Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase

Scheibe, DN, Sang, BC, Mol, CD, Wilson, KP, Dougan, DR, Snell, GP, Skene, RJ, Schneider, TR, Kraus, ML, Zou, H

J. Biol. Chem. 2004
29704617 The role of small molecule Kit protein-tyrosine kinase inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
10224103 Inhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region

Ghosh, I, Ma, Y, Wang, X, Longley, BJ, Regan, L, Cunningham, ME

J. Biol. Chem. 1999
9438854 Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors

Kitamura, Y, Muhammad Tunio, G, Kanakura, Y, Matsuzawa, Y, Hanada, M, Moriyama, Y, Isozaki, K, Nishida, T, Hashimoto, K, Ishiguro, S, Kawano, K, Takeda, M, Kurata, A, Hirota, S, Shinomura, Y

Science 1998
7691885 Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product

Kitamura, Y, Kanakura, Y, Kanayama, Y, Matsuzawa, Y, Sugahara, H, Tono, T, Tsujimura, T, Butterfield, JH, Koshimizu, U, Ashman, LK, Kitayama, H, Furitsu, T, Ikeda, H

J. Clin. Invest. 1993
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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