Ligand-independent dimerization of KIT juxtamembrane domain mutants

Stable Identifier
R-HSA-9669906
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
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Ligand-independent dimerization of KIT juxtamembrane domain mutants
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Mutations of exon 11 of KIT are common initiating events in the onset of gastrointestinal stromal tumors (GIST), and also occur at lower frequency in other cancers (reviewed in Lasota and Miettinen, 2006; Roskoski, 2018). Mutations in exon 11 disrupt the juxtamembrane region of the protein that plays an autoinhibitory role by inserting into the kinase site, disrupting the activated structure (Ma et al, 1999; Chan et al, 2003; Mol et al, 2004; reviewed by Roskoski, 2018; Yuzawa et al, 2007). Mutations in exon 11 include point mutations as well as small deletions, insertions and indels, and result in proteins that can dimerize in a ligand-independent fashion, resulting in constitutive activation of the protein (Tsujimura et al, 1994; Kitayama et al, 1995; Hirota et al, 1998; Furitsu et al, 1993).
Literature References
PubMed ID Title Journal Year
12697809 Autoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane region

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

Mol. Cell. Biol. 2003
15123710 Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase

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

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
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
17662946 Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor

Yuzawa, S, Opatowsky, Y, Zhang, Z, Mandiyan, V, Lax, I, Schlessinger, J

Cell 2007
10224103 Inhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region

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

J. Biol. Chem. 1999
17193822 KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs)

Lasota, J, Miettinen, M

Semin Diagn Pathol 2006
7530509 Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines

Kitayama, H, Kanakura, Y, Furitsu, T, Tsujimura, T, Oritani, K, Ikeda, H, Sugahara, H, Mitsui, H, Kanayama, Y, Kitamura, Y, Matsuzawa, Y

Blood 1995
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
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Functional status

Gain of function of juxtamembrane 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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