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.
Rieken, M, Xylinas, E, Klatte, T, Shariat, SF, Rouprêt, M, Elemento, O, Clozel, T, Zhuang, D, Krzywinski, M, de Martino, M
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
guanyl-nucleotide exchange factor activity of p-6Y-ERBB2 TMD/JMD mutants:Ligand-Activated p-EGFR,p-ERBB3,(p-ERBB4):p-SHC1:GRB2:SOS1 [plasma membrane]
Gain of function of p-6Y-ERBB2 TMD/JMD mutants:Ligand-Activated p-EGFR,p-ERBB3,(p-ERBB4):p-SHC1:GRB2:SOS1 [plasma membrane]
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