PI3K bound to phosphorylated heterodimers of ERBB2 ECD mutants and EGFR converts PIP2 to PIP3

Stable Identifier
R-HSA-9665407
Type
Reaction [transition]
Species
Homo sapiens
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ERBB2 G309E and ERBB2 S310F activate PI3K/AKT signaling, demonstrated by activating phosphorylation of AKT1 (Greulich et al. 2012). It is assumed that phosphorylated heterodimers of ERBB2 ECD mutants and EGFR, like the wild type heterodimers of ERBB2 and EGFR, can bind to the GRB2:GAB1 complex, leading to recruitment of the PI3K complex, which results in conversion of PIP2 to PIP3 and activation of the AKT signaling.

Literature References
PubMed ID Title Journal Year
23220880 Activating HER2 mutations in HER2 gene amplification negative breast cancer

Bose, R, Kavuri, SM, Searleman, AC, Shen, W, Shen, D, Koboldt, DC, Monsey, J, Goel, N, Aronson, AB, Li, S, Ma, CX, Ding, L, Mardis, ER, Ellis, MJ

Cancer Discov 2013
22908275 Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2

Greulich, H, Kaplan, B, Mertins, P, Chen, TH, Tanaka, KE, Yun, CH, Zhang, X, Lee, SH, Cho, J, Ambrogio, L, Liao, R, Imielinski, M, Banerji, S, Berger, AH, Lawrence, MS, Zhang, J, Pho, NH, Walker, SR, Winckler, W, Getz, G, Frank, D, Hahn, WC, Eck, MJ, Mani, DR, Jaffe, JD, Carr, SA, Wong, KK, Meyerson, M

Proc. Natl. Acad. Sci. U.S.A. 2012
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Participant Of
Catalyst Activity
Catalyst Activity
Title
phosphatidylinositol-4,5-bisphosphate 3-kinase activity of p-6Y-ERBB2 ECD mutants:EGF:p-6Y-EGFR:GRB2:GAB1:PI3K [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
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