p21 RAS:GTP p21 RAS:GDP SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with p-EGFR mutants) Authored: Orlic-Milacic, M, 2011-11-04 Based on the wild-type EGFR signaling, it is assumed that the guanine nucleotide exchange factor SOS1 interacts with phosphorylated EGFR mutants through the adaptor protein, GRB2. Upon formation of this complex, SOS1 activates RAS by promoting GDP release and GTP binding. Although this reaction has not been directly confirmed for EGFR cancer mutants, activation of RAF/MAP kinase cascade has been demonstrated, through detection of phosphorylated ERK1/2, in cells expressing EGFR L858R mutant (Sordella et al. 2004, Paez et al. 2004, Shimamura et al. 2005), EGFR E746_A750del mutant (Sordella et al. 2004, Shimamura et al. 2005), EGFR L747_P753delinsS mutant (Sordella et al. 2004) and EGFR E746_A750del;T790M double mutant (Shimamura et al. 2005). Edited: D'Eustachio, P, 2011-11-07 Edited: Matthews, L, 2011-11-07 Edited: Wu, G, 2011-11-07 Pubmed15118125 Pubmed15284455 Pubmed16024644 Reactome Database ID Release 431225951 Reactome, http://www.reactome.org ReactomeREACT_116154 Reviewed: Greulich, H, 2011-11-15 Reviewed: Savas, S, 2011-11-15