Trans-autophosphorylation of activated ligand-responsive EGFR mutant dimers Authored: Orlic-Milacic, M, 2011-11-04 EC Number: 2.7.10 Edited: D'Eustachio, P, 2011-11-07 Edited: Matthews, L, 2011-11-07 Edited: Wu, G, 2011-11-07 Pubmed15284455 Pubmed16777603 Pubmed17177598 Pubmed17349580 Reactome Database ID Release 431169421 Reactome, http://www.reactome.org ReactomeREACT_115772 Reviewed: Greulich, H, 2011-11-15 Reviewed: Savas, S, 2011-11-15 The cytoplasmic domain of EGFR contains tyrosine, serine and threonine phosphorylation sites. Activation of ligand-responsive EGFR mutants through spontaneous or EGF-induced dimerization results in trans-autophosphorylation of 5 tyrosine residues (Y992, Y1068, Y1086, Y1148 and Y1173), which enables constitutive receptor signaling as it provides specific binding sites for cytosolic target proteins involved in signal transduction (Zhang et al. 2006, Yun et al. 2007, Sordella et al. 2004, Lee et al. 2006). Tyrosine residue Y1045, involved in EGFR down-regulation, is usually phosphorylated in ligand-responsive EGFR mutants (Sordella et al. 2004, Lee et al. 2006). The exact phosphorylation pattern has not been examined for each mutant, but is assumed to closely follow, based on existing experimental evidence, the trans-autophosphorylation pattern of the wild-type EGFR. has a Stoichiometric coefficient of 12 Ligand-responsive p-6Y-EGFR mutant dimers Active dimers of ligand-responsive EGFR mutants