Constitutive phosphorylation of kinase domain KIT mutants

Stable Identifier
R-HSA-9669890
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
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Constitutive phosphorylation of kinase domain KIT mutants
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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

Corless, CL, Barnett, CM, 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

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

Blood 1994
9438854 Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors

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

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

J. Clin. Invest. 1993
Participants
Input
Output
Participates
as an event of
Catalyst Activity

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

Physical Entity
kinase domain KIT mutants [plasma membrane] (Homo sapiens)
Activity
protein tyrosine kinase activity (GO:0004713)
Functional status

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

Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Cross References
Mondo
Authored
Rothfels, K  (2020-04-01)
Reviewed
Serrano, C  (2020-03-13)
García-Valverde, A  (2020-03-13)
Pilco-Janeta, D  (2020-03-13)
Created
Rothfels, K  (2019-12-03)
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