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Weak binding to E3 ubiquitin ligase c‐Cbl increases EGFRvA protein stability
Author(s) -
Song Fei,
Zhou Min,
Wang Biao,
Shi Bizhi,
Jiang Hua,
Zhang Jiqin,
Li Zonghai
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12166
Subject(s) - ubiquitin ligase , ubiquitin , chemistry , epidermal growth factor receptor , grb2 , gene isoform , ubiquitin protein ligases , dna ligase , mediator , plasma protein binding , microbiology and biotechnology , phosphorylation , receptor , signal transducing adaptor protein , biochemistry , biology , enzyme , gene
Recently, we have identified a novel epidermal growth factor receptor isoform (EGFRvA), which has higher tumor‐promoting capacity than EGFR. However, the underlying mechanism is not well understood. Here, we demonstrate that EGFRvA is more stable than EGFR. Interestingly, we observe that EGFRvA binds less to E3 ubiquitin ligase c‐Cbl than EGFR does, although Y1045, a direct binding site of c‐Cbl, is well phosphorylated in both of them. Further study reveals that EGFRvA cannot bind to Grb2, an important binding mediator between EGFR and c‐Cbl. Thus, our study finds that EGFRvA is more stable than EGFR because of its decreased binding to c‐Cbl.