p-KIT mutants:GRB2:SOS catalyzes nucleotide exchange on RAS

Stable Identifier
Reaction [transition]
Homo sapiens
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Activation of the MAP kinase signaling pathway downstream of oncogenic KIT mutants, as evidenced by the presence of phosphorylated ERK proteins, likely depends on the SOS-mediated nucleotide exchange of GDP for GTP on RAS, as is the case for the wild-type receptor (Frost et al, 2002; Chi et al, 2010; Garner et al, 2014; Monsel et al, 2010; Obata et al, 2017; 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
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
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
25239608 Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients

Anjum, R, Heinrich, MC, Ketzer, J, Bauer, S, Zhu, M, Zhou, T, Serrano, C, Song, Y, Fletcher, JA, Schrock, A, Ning, Y, Eilers, G, Wardwell, S, Gozgit, JM, Kohlmann, A, Garner, AP, Rivera, VM, Vodala, S, Clackson, T, Wang, F

Clin. Cancer Res. 2014
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
19802003 c-Kit mutants require hypoxia-inducible factor 1alpha to transform melanocytes

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

Oncogene 2010
Catalyst Activity

guanyl-nucleotide exchange factor activity of p-KIT mutants:GRB2:SOS [plasma membrane]

Normal reaction
Functional status

Gain of function of p-KIT mutants:GRB2:SOS [plasma membrane]

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