SH3KBP1-binding protein 1 prevents epidermal growth factor receptor degradation by the interruption of c-Cbl-CIN85 complex.
SH3KBP1-binding protein 1 prevents epidermal growth factor receptor degradation by the interruption of c-Cbl-CIN85 complex.
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DOI：
10.1002/cbf.1792
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发表时间：
2011-10
影响因子：
3.6
通讯作者：
Geng JG
中科院分区：
文献类型：
--
作者：
Feng L;Wang JT;Jin H;Qian K;Geng JG
Cbl相互作用蛋白（CIN 85）与c-Cbl的结合对表皮生长因子受体（EGFR）的内吞和降解具有重要作用。CIN 85的c-Cbl和SH 3结构域中的脯氨酸-精氨酸基序PXXXPR对于这种相互作用是必不可少的。在这里，我们证明了SH 3 KBP 1结合蛋白1（SHKBP 1），它也包含两个PXXXPR基序，组成型结合到CIN 85的SH 3结构域。重要的是，SHKBP 1的结合阻止了CIN 85与c-Cbl的相互作用，并抑制了CIN 85向含有EGFR的囊泡的易位，从而减少了EGFR降解并增强了EGF诱导的SRE转录活性。因此，SHKBP 1可能通过阻断c-Cbl-CIN 85复合物，抑制EGFR降解，从而促进EGFR信号通路。
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 SRE transcription activity. Therefore, our results indicated that SHKBP1 could promote EGFR signaling pathway by interrupting c-Cbl-CIN85 complex and inhibiting EGFR degradation.