Binding of SHC1 to p-6Y-EGFR mutants

Stable Identifier
Reaction [binding]
Homo sapiens
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SHC1 (Src homology 2 domain-containing transforming protein) is known to bind two phosphorylated tyrosine docking sites of EGFR: Y1148 and Y1173 (corresponding to Y1172 and Y1197 when counting from the first amino acid of EGFR precursor, before the cleavage of the 24-amino acid signal peptide at the N-terminus takes place). Phosphorylation of Y1173 tyrosine residue was directly demonstrated in the following EGFR cancer mutants: EGFR L858R mutant (Sordella et al. 2004, Greulich et al. 2005); EGFR G719S mutant (Greulich et al. 2005); EGFR L747_P753delinsS mutant (Sordella et al. 2004); EGFR L747_A750delinsP (Greulich et al. 2005); EGFRvIII mutant (Han et al. 2006, Grandal et al. 2007); 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). Phosphorylation of Y1148 was shown in EGFRvIII mutant (Huang et al. 2007).
Besides EGFR L858R mutant, which was directly shown to bind SHC1 (Greulich et al. 2005), binding of SHC1 was not tested in other EGFR cancer mutants. Nonetheless, it is assumed that SHC1 binds EGFR cancer mutants in the same way it binds wild-type EGFR.

Literature References
PubMed ID Title Journal Year
16969069 Hypophosphorylation of residue Y1045 leads to defective downregulation of EGFRvIII

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

Cancer Biol Ther 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
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
17372273 EGFRvIII escapes down-regulation due to impaired internalization and sorting to lysosomes

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

Carcinogenesis 2007
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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