Reactome | RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants

RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants

Stable Identifier

R-HSA-9665700

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants

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Activation of downstream RAS signaling was shown for ERBB2 S653C (de Martino et al. 2014) and ERBB2 R678Q (Bose et al. 2013, de Martino et al. 2014) through activating tyrosine phosphorylation on ERKs (MAPK1 and MAPK3) and SHC1. It is assumed that heterodimers of ERBB2 TMD/JMD mutants, like the wild type ERBB2 heterodimers, bind to and phosphorylate SHC1, leading to the recruitment of the GRB2:SOS1 complex and activation of RAS through guanyl nucleotide exchange.

Literature References

PubMed ID	Title	Journal	Year
24971884	Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinib de Martino, M, Zhuang, D, Klatte, T, Rieken, M, Rouprêt, M, Xylinas, E, Clozel, T, Krzywinski, M, Elemento, O, Shariat, SF	Cancer Biol. Ther.	2014
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