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Cell Biochem Funct. 2011 Oct;29(7):589-96. doi: 10.1002/cbf.1792. Epub 2011 Aug 9.

SH3KBP1-binding protein 1 prevents epidermal growth factor receptor degradation by the interruption of c-Cbl-CIN85 complex.

Author information

1
College of Lifescience, Zhejiang University, Hangzhou, Zhejiang, China.

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.

PMID:
21830225
PMCID:
PMC4534006
DOI:
10.1002/cbf.1792
[Indexed for MEDLINE]
Free PMC Article

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