Phosphorylated KIT mutants bind PI3K

Stable Identifier
R-HSA-9670431
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane, cytosol, extracellular region
ReviewStatus
5/5
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Phosphorylated KIT mutants bind PI3K
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PI3K-mediated signaling has been demonstrated downstream of a number of oncogenic KIT mutants, including extracellular, juxtamembrane and kinase domain mutants (Kemmer et al, 2004; Nakai et al, 2005; Hara et al, 2017; Obata et al, 2017; Duensing et al, 2004; Tarn et al, 2006; Rossi et al, 2006; Bauer et al, 2007; Bosbach et al, 2017; Zhu et al, 2007). In this pathway, KIT mutants are shown directly recruiting PI3K; pathway activation may also involve indirect recruitment through GRB2:GAB2, as in the wild-type pathway (reviewed in Lennnartsson and Roonstrand, 2012; Corless et al, 2011).
Literature References
PubMed ID Title Journal Year
23073628 Stem cell factor receptor/c-Kit: from basic science to clinical implications

Lennartsson, J, Rönnstrand, L

Physiol. Rev. 2012
14695343 KIT mutations are common in testicular seminomas

Kemmer, K, Corless, CL, Fletcher, JA, McGreevey, L, Haley, A, Griffith, D, Cummings, OW, Wait, C, Town, A, Heinrich, MC

Am. J. Pathol. 2004
22089421 Gastrointestinal stromal tumours: origin and molecular oncology

Corless, CL, Barnett, CM, Heinrich, MC

Nat. Rev. Cancer 2011
16707477 Therapeutic effect of imatinib in gastrointestinal stromal tumors: AKT signaling dependent and independent mechanisms

Tarn, C, Skorobogatko, YV, Taguchi, T, Eisenberg, B, von Mehren, M, Godwin, AK

Cancer Res. 2006
28192400 Oncogenic signaling by Kit tyrosine kinase occurs selectively on the Golgi apparatus in gastrointestinal stromal tumors

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

Oncogene 2017
28403213 M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells

Hara, Y, Obata, Y, Horikawa, K, Tasaki, Y, Suzuki, K, Murata, T, Shiina, I, Abe, R

PLoS ONE 2017
16188233 KIT (c-kit oncogene product) pathway is constitutively activated in human testicular germ cell tumors

Nakai, Y, Nonomura, N, Oka, D, Shiba, M, Arai, Y, Nakayama, M, Inoue, H, Nishimura, K, Aozasa, K, Mizutani, Y, Miki, T, Okuyama, A

Biochem. Biophys. Res. Commun. 2005
16908864 Oncogenic Kit signaling and therapeutic intervention in a mouse model of gastrointestinal stromal tumor

Rossi, F, Ehlers, I, Agosti, V, Socci, ND, Viale, A, Sommer, G, Yozgat, Y, Manova, K, Antonescu, CR, Besmer, P

Proc. Natl. Acad. Sci. U.S.A. 2006
17452978 KIT oncoprotein interactions in gastrointestinal stromal tumors: therapeutic relevance

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

Oncogene 2007
28923937 Direct engagement of the PI3K pathway by mutant KIT dominates oncogenic signaling in gastrointestinal stromal tumor

Bosbach, B, Rossi, F, Yozgat, Y, Loo, J, Zhang, JQ, Berrozpe, G, Warpinski, K, Ehlers, I, Veach, D, Kwok, A, Manova, K, Antonescu, CR, DeMatteo, RP, Besmer, P

Proc. Natl. Acad. Sci. U.S.A. 2017
17546049 KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway

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

Oncogene 2007
Participants
Input
Output
Participates
as an event of
Normal reaction
Direct recruitment of PI3K to p-KIT (Homo sapiens)
Functional status

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

Normal Entity
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  (2019-12-09)
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