KIT mutants bind GRB2-SOS

Stable Identifier
Reaction [binding]
Homo sapiens
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A number of activating extracellular-, juxtamembrane- and kinase-domain KIT mutants are believed to signal through the RAS/MAP kinase cascade, as assessed by the presence of phospho-ERK1 and 2 (also known as MAPK3 and MAPK1). Although the pathway has not been studied in detail, signaling downstream of KIT mutants likely involves recruitment of GRB2:SOS1, as is the case for the wild-type receptor Frost et al, 2002; Garner et al, 2014; Monsel et al, 2010; Obata et al, 2017; Chi et al, 2010; Ran et al, 2015; Serrano et al, 2015; Zhu et al, 2007; reviewed in Abbaspour Babaei et al, 2016; Lennartsson and Roonstrand, 2012).
Literature References
PubMed ID Title Journal Year
27536065 Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells

Ahmadipour, F, Abbaspour Babaei, M, Huri, HZ, Kamalidehghan, B, Saleem, M

Drug Des Devel Ther 2016
24687822 KRAS and KIT Gatekeeper Mutations Confer Polyclonal Primary Imatinib Resistance in GI Stromal Tumors: Relevance of Concomitant Phosphatidylinositol 3-Kinase/AKT Dysregulation

Corless, CL, Morgan, JA, Fletcher, JA, Beadling, C, Heinrich, MC, Mariño-Enríquez, A, Demetri, GD, Ravegnini, G, Bertagnolli, MM, Lee, JC, Wang, Y, Serrano, C

J. Clin. Oncol. 2015
23073628 Stem cell factor receptor/c-Kit: from basic science to clinical implications

Rönnstrand, L, Lennartsson, J

Physiol. Rev. 2012
20927104 ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours

Dewell, S, Antonescu, CR, Chen, Y, Maki, RG, Zhang, L, Sawyers, CL, Allis, CD, Shamu, T, Guo, X, Fletcher, JA, Zheng, D, Chi, P, Wongvipat, J

Nature 2010
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
12481435 Juxtamembrane mutant V560GKit is more sensitive to Imatinib (STI571) compared with wild-type c-kit whereas the kinase domain mutant D816VKit is resistant

Frost, MJ, Ferrao, PT, Hughes, TP, Ashman, LK

Mol. Cancer Ther. 2002
17452978 KIT oncoprotein interactions in gastrointestinal stromal tumors: therapeutic relevance

Fletcher, CD, Ou, WB, Cohen, PS, Zhu, MJ, Demetri, GD, Fletcher, JA

Oncogene 2007
19802003 c-Kit mutants require hypoxia-inducible factor 1alpha to transform melanocytes

Dumaz, N, Ortonne, N, Bensussan, A, Bagot, M, Monsel, G

Oncogene 2010
25572173 Combined inhibition of MAP kinase and KIT signaling synergistically destabilizes ETV1 and suppresses GIST tumor growth

Antonescu, CR, Chen, Y, Besmer, P, Mellinghoff, IK, Sirota, I, Xie, Y, Taguchi, T, Zhu, S, Cao, Z, Kaufmann, MC, Shukla, S, Rossi, F, Chi, P, Ran, L, Tap, WD, Wongvipat, J, Gao, D, Murphy, D, Chen, Y

Cancer Discov 2015
Normal reaction
Functional status

Gain of function of p7Y-KIT kinase, extracellular and juxtamembrane domain dimers [plasma membrane]

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