Reactome | RAS guanyl nucleotide exchange mediated by the p-6Y- ERBB2 ECD mutants:EGF:p-6Y-EGFR:p-SHC1:GRB2:SOS1

RAS guanyl nucleotide exchange mediated by the p-6Y- ERBB2 ECD mutants:EGF:p-6Y-EGFR:p-SHC1:GRB2:SOS1

Stable Identifier

R-HSA-9665404

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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RAS guanyl nucleotide exchange mediated by the p-6Y- ERBB2 ECD mutants:EGF:p-6Y-EGFR:p-SHC1:GRB2:SOS1

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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 recruit the GRB2:SOS1 complex through phosphorylated SHC1, leading to guanyl nucleotide exchange on RAS and activation of RAS signaling.

Literature References

PubMed ID	Title	Journal	Year
22908275	Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2 Walker, SR, Greulich, H, Pho, NH, Banerji, S, Berger, AH, Lawrence, MS, Getz, G, Frank, D, Tanaka, KE, Chen, TH, Mani, DR, Liao, R, Imielinski, M, Winckler, W, Lee, SH, Meyerson, M, Hahn, WC, Wong, KK, Ambrogio, L, Kaplan, B, Cho, J, Mertins, P, Carr, SA, Jaffe, JD, Zhang, X, Eck, MJ, Yun, CH, Zhang, J	Proc. Natl. Acad. Sci. U.S.A.	2012
23220880	Activating HER2 mutations in HER2 gene amplification negative breast cancer Bose, R, Shen, W, Aronson, AB, Goel, N, Koboldt, DC, Li, S, Searleman, AC, Ma, CX, Ellis, MJ, Shen, D, Ding, L, Monsey, J, Mardis, ER, Kavuri, SM	Cancer Discov	2013