PLCG1 binds to ligand-responsive p-6Y-EGFR mutants

Stable Identifier
Reaction [binding]
Homo sapiens
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Tyrosine residue Y992 (corresponding to Y1016 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), a docking site for PLC-gamma 1 (PLCG1), is phosphorylated in EGFR cancer mutants and expected to recruit PLC-gamma 1 in the same way as the wild-type EGFR receptor. Phosphorylation of Y992 (corresponding to Y1016 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) has been directly demonstrated for the following EGFR cancer mutants: EGFR L858R mutant (Sordella et al. 2004, Choi et al. 2007); EGFR G719S mutant (Choi et al. 2007); EGFR L747_P753delinsS mutant (Sordella et al. 2004, Choi et ak, 2007); EGFR L861Q mutant (Choi et al. 2007); EGFRvIII mutant (Grandal et al. 2007); EGFR A289V mutant (Lee et al. 2006); EGFR D770_N771insNPG mutant (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
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
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
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
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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