Binding of CBL to ligand-responsive p-6Y-EGFR mutants

Stable Identifier
R-HSA-1225949
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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CBL binds to phosphorylated tyrosine Y1045 residue of EGFR cancer mutants. Phosphorylation of Y1045 (corresponding to Y1069 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 in the following EGFR cancer mutants: EGFR L858R mutant (Greulich et al. 2005, Choi et al. 2007); EGFR G719S mutant (Sordella et al. 2004, Greulich et al. 1005, Choi et al. 2007); EGFR L747_P753delinsS mutant (Sordella et al. 2004, Choi et al. 2007); EGFR L747_A750delinsP mutant (Greulich et al. 2005); EGFR L861Q mutant (Choi 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 D770_N771insNPG mutant (Greulich et al. 2005; Xu et al. 2007); EGFR V738_K739insKIPVAI mutant (Xu et al. 2007); EGFR M766_A767insASV mutant (Xu et al. 2007). Very little if any phosphorylation of Y1045 was shown in EGFR T263P mutant (Lee et al. 2006) and EGFR D770_N771insNPH mutant (Xu et al. 2007). Direct binding of CBL was demonstrated for the EGFR L858R mutant (Yang et al. 2006, Padron et al. 2007) and EGFR E746_A750del mutant (Padron et al. 2007). In EGFRvIII mutant, Y1045 (Y1069) is not phosphorylated (Han et al. 2006, Grandal et al. 2007). Han et al. detected no CBL binding to EGFRvIII mutant (Han et al. 2006), while Grandal et al. detected very little binding, which they explained by indirect recruitment of CBL to EGFRvIII through GRB2 (Grandal 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

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
16969069 Hypophosphorylation of residue Y1045 leads to defective downregulation of EGFRvIII

Han, W, Zhang, T, Yu, H, Foulke, JG, Tang, CK

Cancer Biol Ther 2006
16953218 EGF-independent activation of cell-surface EGF receptors harboring mutations found in gefitinib-sensitive lung cancer

Choi, SH, Mendrola, JM, Lemmon, MA

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

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

PLoS Med 2005
17699773 Epidermal growth factor receptors with tyrosine kinase domain mutations exhibit reduced Cbl association, poor ubiquitylation, and down-regulation but are efficiently internalized

Padrón, D, Sato, M, Shay, JW, Gazdar, AF, Minna, JD, Roth, MG

Cancer Res 2007
15284455 Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways

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

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

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

Br J Cancer 2007
17372273 EGFRvIII escapes down-regulation due to impaired internalization and sorting to lysosomes

Grandal, MV, Zandi, R, Pedersen, MW, Willumsen, BM, van Deurs, B, Poulsen, HS

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

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

Cancer Res 2006
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created