Trans-autophosphorylation of EGFRvIII mutant dimers

Stable Identifier
R-HSA-1248655
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane, cytosol
ReviewStatus
5/5
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Trans-autophosphorylation of EGFRvIII mutant dimers
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Upon dimerization, EGFRvIII mutants trans-autophosphorylate on tyrosine residues Y1016 i.e. Y992 in the mature protein, Y1092 i.e. Y1068 in the mature protein, Y1110 i.e. Y0186 in the mature protein, Y1172 i.e. Y1148 in the mature protein and Y1197 i.e. Y1173 in the mature protein, while the tyrosine residue Y1069 i.e. Y1045 in the mature protein, a docking site for CBL, remains either unphosphorylated or hypophosphorylated, allowing EGFRvIII to activate downstream signaling cascades while escaping downregulation.
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
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
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein tyrosine kinase activity of EGFRvIII mutant dimer [plasma membrane]

Physical Entity
EGFRvIII mutant dimer [plasma membrane] (Homo sapiens)
Activity
protein tyrosine kinase activity (GO:0004713)
Normal reaction
EGFR autophosphorylation (Homo sapiens)
Functional status

Gain of function of EGFRvIII mutant dimer [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Orlic-Milacic, M  (2011-11-04)
Reviewed
Greulich, H  (2011-11-15)
Savas, S  (2011-11-15)
Created
Orlic-Milacic, M  (2011-04-11)
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