title: Weak binding to E3 ubiquitin ligase c-Cbl increases EGFRvA protein stability.
abstract: 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.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Bizhi
authors.initials: B
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Jiqin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Zonghai
authors.initials: Z
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D055550:Protein Stability; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*
chemical_list: D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D020033:Protein Isoforms; D050721:Proto-Oncogene Proteins c-cbl; C512478:EGFR protein, human; D066246:ErbB Receptors; C067419:CBL protein, human
keywords: EGFR; EGFRvA; Grb2; c-Cbl; protein stability