Trans-autophosphorylation of activated ligand-responsive EGFR mutant dimers

Stable Identifier
R-HSA-1169421
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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.

Literature References
PubMed ID Title Journal Year
15284455 Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways

Sordella, R, Bell, DW, Haber, DA, Settleman, J

Science 2004
17177598 Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain

Lee, JC, Vivanco, I, Beroukhim, R, Huang, JHY, Feng, WL, DeBiasi, RM, Yoshimoto, K, King, JC, Nghiemphu, P, Yuza, Y, Xu, Q, Greulich, H, Thomas, RK, Paez, JG, Peck, TC, Linhart, DJ, Glatt, KA, Getz, G, Onofrio, R, Ziaugra, L, Levine, RL, Gabriel, S, Kawaguchi, T, O'Neill, K, Khan, H, Liau, LM, Nelson, SF, Rao, PN, Mischel, P, Pieper, RO, Cloughesy, T, Leahy, DJ, Sellers, WR, Sawyers, CL, Meyerson, M, Mellinghoff, IK

PLoS Med 2006
17349580 Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity

Yun, CH, Boggon, TJ, Li, Y, Woo, MS, Greulich, H, Meyerson, M, Eck, MJ

Cancer Cell 2007
16777603 An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor

Zhang, X, Gureasko, J, Shen, K, Cole, PA, Kuriyan, J

Cell 2006
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
protein tyrosine kinase activity of Active dimers of ligand-responsive EGFR mutants [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created
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