Binding of GRB2:SOS1 complex to phosphorylated ligand-responsive EGFR mutants

Stable Identifier
Reaction [binding]
Homo sapiens
Binding of GRB2:SOS1 to ligand-responsive p-6Y-EGFR mutants
Locations in the PathwayBrowser
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Direct binding of GRB2:SOS1 complex to phosphorylated homodimers of EGFR cancer mutants has not been tested. GRB2 binds to phosphorylated tyrosine residues Y1068 and Y1086 (corresponding to Y1092 and Y1110, respectively, when counting from the first amino acid of the EGFR precursor, prior to cleavage of the 24-amino acid signal peptide at the N-terminus). Phosphorylation of Y1068 (i.e. Y1092) has been directly demonstrated in the following EGFR cancer mutants: EGFR L858R mutant (Sordella et al. 2004, Lynch et al. 2004, Greulich et al. 2005, Yang et al. 2006, Choi et al. 2007); EGFR G719S mutant (Greulich et al. 2005, Choi et al. 2007); EGFR L747_P753insS mutant (Sordella et al. 2004, Lynch et al. 2004, Choi et al. 2007); EGFR L747_A750delinsP (Greulich et al. 2005); EGFR L747_S752del mutant (Pao et al. 2004); EGFR L861Q mutant (Lee et al. 2006, Yang et al. 2006); EGFRvIII mutant (Huang et al. 2007); EGFR A289V mutant (Lee et al. 2006); EGFR G598V mutant (Lee et al. 2006); EGFR R108K mutant (Lee et al. 2006); EGFR T263P mutant (Lee et al. 2006); EGFR D770_N771insNPG mutant (Greulich et al. 2005, Xu et al. 2007); EGFR N771_H773dup mutant (Xu et al. 2007); EGFR K739_I744dup mutant (Xu et al. 2007); EGFR A767_V769dup mutant (Xu et al. 2007).
Literature References
PubMed ID Title Journal Year
17177598 Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain

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

PLoS Med 2006
15329413 EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib

Varmus, H, Kupfer, D, Rusch, V, Miller, V, Politi, K, Kris, M, Zakowski, M, Heelan, R, Mardis, E, Fulton, L, Wilson, R, Singh, B, Sarkaria, I, Pao, W, Doherty, J

Proc Natl Acad Sci U S A 2004
15118073 Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib

Bell, DW, Lynch, TJ, Harris, PL, Brannigan, BW, Supko, JG, Gurubhagavatula, S, Louis, DN, Christiani, DC, Okimoto, RA, Haber, DA, Haluska, FG, Haserlat, SM, Settleman, J, Sordella, R

N Engl J Med 2004
16953218 EGF-independent activation of cell-surface EGF receptors harboring mutations found in gefitinib-sensitive lung cancer

Mendrola, JM, Choi, SH, Lemmon, MA

Oncogene 2007
16187797 Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants

Feng, WL, Hahn, WC, Chen, TH, Meyerson, M, Frank, DA, Sellers, WR, Jänne, PA, Alvarez, JV, Greulich, H, Bulmer, SE, Zappaterra, M

PLoS Med 2005
15284455 Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways

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

Science 2004
17712310 Sensitivity of epidermal growth factor receptor and ErbB2 exon 20 insertion mutants to Hsp90 inhibition

Kim, YS, Lee, MJ, Beebe, K, Soga, S, Neckers, LM, Trepel, J, Xu, W

Br J Cancer 2007
16849543 Association with HSP90 inhibits Cbl-mediated down-regulation of mutant epidermal growth factor receptors

Qu, S, Perez-Tores, M, Sawai, A, Yang, S, Arteaga, CL, Solit, DB, Rosen, N

Cancer Res 2006
17646646 Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma

Bonavia, R, Huang, PH, White, FM, Furnari, FB, Brewer, ZE, Mukasa, A, Cavenee, WK, Flynn, RA

Proc Natl Acad Sci U S A 2007
Normal reaction
Functional status

Gain of function of Ligand-responsive p-6Y-EGFR mutant dimers [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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