RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 ECD mutants and EGFR through GRB2

Stable Identifier
R-HSA-9665408
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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RAS signaling is activated dowsntream of ERBB2 ECD mutants ERBB2 G309A (Bose et al. 2013), ERBB2 G309E (Greulich et al. 2012) and ERBB2 S310F (Greulich et al. 2012), as evidenced by activating phosphorylation of ERKs (MAPK1 and MAPK3). It is assumed that phosphorylated heterodimers of ERBB2 ECD mutants and EGFR, like phosphorylated heterodimers of the wild type ERBB2, can directly recruit the GRB2:SOS1 complex, leading to guanyl nucleotide exchange on RAS and activation of RAS 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
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
Ras guanyl-nucleotide exchange factor activity of p-6Y-ERBB2 ECD mutants:EGF:p-6Y-EGFR:GRB2:SOS1 [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
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