title: SH3KBP1-binding protein 1 prevents epidermal growth factor receptor degradation by the interruption of c-Cbl-CIN85 complex.
abstract: The binding of Cbl-interacting protein of 85 kDa (CIN85) to c-Cbl is important to endocytosis and degradation of epidermal growth factor receptor (EGFR). The proline-arginine motif PXXXPR in c-Cbl and SH3 domains of CIN85 are essential to this interaction. Here, we demonstrated that SH3KBP1-binding protein 1 (SHKBP1), which also contains two PXXXPR motifs, constitutively bound to SH3 domains of CIN85. Importantly, the binding of SHKBP1 prevented the interaction of CIN85 with c-Cbl and inhibited the translocation of CIN85 to EGFR-containing vesicles, thus reducing EGFR degradation and enhancing EGF-induced serum response element transcription activity. Therefore, our results indicated that SHKBP1 could promote EGFR signaling pathway by interrupting c-Cbl-CIN85 complex and inhibiting EGFR degradation.
authors.affiliation: College of Lifescience, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Feng
authors.forename: Jin-Tao
authors.initials: JT
authors.lastname: Wang
authors.forename: Hongchuan
authors.initials: H
authors.lastname: Jin
authors.forename: Kaixian
authors.initials: K
authors.lastname: Qian
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Geng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017930:Genes, Reporter; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D046912:Multiprotein Complexes; C433810:SH3KBP1 protein, human; D004815:Epidermal Growth Factor; D050721:Proto-Oncogene Proteins c-cbl; D066246:ErbB Receptors; C067419:CBL protein, human