p-EGFR mutants dimer Binding of SHC1 to p-EGFR mutants Authored: Orlic-Milacic, M, 2011-11-04 Edited: D'Eustachio, P, 2011-11-07 Edited: Matthews, L, 2011-11-07 Edited: Wu, G, 2011-11-07 Pubmed15284455 Pubmed16187797 Pubmed16969069 Pubmed17372273 Pubmed17646646 Pubmed17712310 Reactome Database ID Release 431225947 Reactome, http://www.reactome.org ReactomeREACT_116063 Reviewed: Greulich, H, 2011-11-15 Reviewed: Savas, S, 2011-11-15 SHC1 (Src homology 2 domain-containing transforming protein) is known to bind two phosphorylated tyrosine docking sites of EGFR: Y1148 and Y1173 (corresponding to Y1172 and Y1197 when counting from the first amino acid of EGFR precursor, before the cleavage of the 24-amino acid signal peptide at the N-terminus takes place). Phosphorylation of Y1173 tyrosine residue was directly demonstrated in the following EGFR cancer mutants: EGFR L858R mutant (Sordella et al. 2004, Greulich et al. 2005); EGFR G719S mutant (Greulich et al. 2005); EGFR L747_P753delinsS mutant (Sordella et al. 2004); EGFR L747_A750delinsP (Greulich et al. 2005); EGFRvIII mutant (Han et al. 2006, Grandal et al. 2007); EGFR D770_N771insNPG mutant (Greulich et al. 2005, Xu et al. 2007); EGFR D770_N771insNPH mutant (Xu et al. 2007); EGFR V738_K739insKIPVAI mutant (Xu et al. 2007); EGFR M766_A767insASV mutant (Xu et al. 2007). Phosphorylation of Y1148 was shown in EGFRvIII mutant (Huang et al. 2007). <br> Besides EGFR L858R mutant, which was directly shown to bind SHC1 (Greulich et al. 2005), binding of SHC1 was not tested in other EGFR cancer mutants. Nonetheless, it is assumed that SHC1 binds EGFR cancer mutants in the same way it binds wild-type EGFR. p-EGFR mutants:SHC1