Constitutive phosphorylation of kinase domain KIT mutants

Stable Identifier
Reaction [transition]
Homo sapiens
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Activating kinase domain mutants of KIT are constitutively active in the absence of ligand and can be tyrosine phosphorylated in the absence of dimerization (Furitsu et al, 1993; Hirota et al, 1998; Tsujimura et al, 1994). These mutations, which are encoded in exons 13, 14 and 17, are present at low frequency in AML, myeloma and germ cell tumors, as well as myeloproliferative disorders and mastocytosis, and occur as primary oe secondary resistance mutations in imatinib-treated gastrointestinal stromal tumors (reviewed in Antonescu, 2006; Roskoski, 2018; Corless et al, 2011).
Literature References
PubMed ID Title Journal Year
22089421 Gastrointestinal stromal tumours: origin and molecular oncology

Barnett, CM, Corless, CL, Heinrich, MC

Nat. Rev. Cancer 2011
17193819 Gastrointestinal stromal tumor (GIST) pathogenesis, familial GIST, and animal models

Antonescu, CR

Semin Diagn Pathol 2006
29704617 The role of small molecule Kit protein-tyrosine kinase inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
7513208 Ligand-independent activation of c-kit receptor tyrosine kinase in a murine mastocytoma cell line P-815 generated by a point mutation

Kitamura, Y, Kanakura, Y, Matsuzawa, Y, Isozaki, K, Morimoto, M, Nomura, S, Furitsu, T, Tsujimura, T

Blood 1994
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
Catalyst Activity

protein tyrosine kinase activity of kinase domain KIT mutants [plasma membrane]

Functional status

Gain of function of kinase domain KIT mutants [plasma membrane]

Disease Entity
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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