JAK2 binds to p-KIT mutants

Stable Identifier
Reaction [binding]
Homo sapiens
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Activation of STAT signaling has been observed downstream of a number of oncogenic KIT mutants, both juxtamembrane and kinase domain mutants, although the biological relevance or each STAT isoform varies between tumor types (Brizzi et al, 1999; Ning et al, 2001; Frost et al, 2002; Growney et al, 2005; Hana et al, 2017; Obata et al, 2017; Duensing et al, 2004; Bauer et al, 2007; Deberry et al, 1997; Ronnstrand, 2004). Although the pathway details haven't been examined in all cases, this likely occurs through the recruitment of JAK2 and SRC family kinases, as is the case for the wild type receptor (reviewed in Lennartsson and Roonstrand, 2012).
Literature References
PubMed ID Title Journal Year
23073628 Stem cell factor receptor/c-Kit: from basic science to clinical implications

Rönnstrand, L, Lennartsson, J

Physiol. Rev. 2012
28192400 Oncogenic signaling by Kit tyrosine kinase occurs selectively on the Golgi apparatus in gastrointestinal stromal tumors

Akieda, Y, Abe, R, Obata, Y, Nishida, T, Esumi, H, Fletcher, JA, Takahashi, T, Tsujimoto, M, Horikawa, K

Oncogene 2017
10358045 STAT protein recruitment and activation in c-Kit deletion mutants

Yarden, Y, Dentelli, P, Pegoraro, L, Rosso, A, Brizzi, MF

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
11369651 Signal transducer and activator of transcription 3 activation is required for Asp(816) mutant c-Kit-mediated cytokine-independent survival and proliferation in human leukemia cells

Arceci, RJ, Li, J, Ning, ZQ

Blood 2001
17546049 KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway

Demetri, GD, Bauer, S, Fletcher, JA, Duensing, A

Oncogene 2007
15790786 Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412

Griffin, JD, Gilliland, DG, Adelsperger, J, Fabbro, D, Clark, JJ, Stone, R, Growney, JD

Blood 2005
Normal reaction
Functional status

Gain of function of KIT mutant dimers:SFKs [plasma membrane]

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