Weak binding to E3 ubiquitin ligase c‐Cbl increases EGFRvA protein stability
Weak binding to E3 ubiquitin ligase c‐Cbl increases EGFRvA protein stability
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DOI：
10.1002/1873-3468.12166
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发表时间：
2016-05
期刊：
影响因子：
3.5
通讯作者：
Fei Song;Min Zhou;Biao Wang;B. Shi;Hua Jiang;Jiqin Zhang;Zonghai Li
中科院分区：
文献类型：
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作者：
Fei Song;Min Zhou;Biao Wang;B. Shi;Hua Jiang;Jiqin Zhang;Zonghai Li
最近，我们发现了一种新型表皮生长因子受体亚型（EGFRvA），它比 EGFR 具有更高的促肿瘤能力。然而，其基本机制尚不清楚。在这里，我们证明 EGFRvA 比 EGFR 更稳定。有趣的是，我们观察到 EGFRvA 与 E3 泛素连接酶 c-Cbl 的结合少于 EGFR，尽管 c-Cbl 的直接结合位点 Y1045 在两者中都被很好地磷酸化。进一步的研究表明，EGFRvA 不能与 Grb2 结合，Grb2 是 EGFR 和 c-Cbl 之间的重要结合介质。因此，我们的研究发现 EGFRvA 比 EGFR 更稳定，因为它与 c-Cbl 的结合减少。
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.