N-Glycosylation of integrin α5 acts as a switch for EGFR-mediated complex formation of integrin α5β1 to α6β4.
N-Glycosylation of integrin α5 acts as a switch for EGFR-mediated complex formation of integrin α5β1 to α6β4.
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DOI：
10.1038/srep33507
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发表时间：
2016-09-19
影响因子：
4.6
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Hang Q;Isaji T;Hou S;Zhou Y;Fukuda T;Gu J
整合素α5β1的N-糖基化参与多种细胞行为。我们先前报道了整合素α5（S3- 5，10 -14）上的calf结构域的N-糖基化对于其在调节细胞增殖中对EGFR信号传导的抑制作用是必不可少的。然而，单个N-糖基化的重要性和潜在的抑制机制仍不清楚。在这里，我们详细描述了S3- 5，10 -14突变体，发现11位（Asn 712）的N-糖基化是细胞生长的关键。与其他单个位点不同，位点11的恢复以与野生型（WT）相似的方式显著抑制细胞生长和EGFR信号传导。从机制上讲，这种N-糖基化抑制了EGF刺激和EGFR二聚化后的反应能力。有趣的是，我们发现这种N-糖基化控制了EGFR与整合素α5β1或α6β4的复合物形成;即，位点11的缺失将EGFR-α5β1转换为EGFR-α6β4，众所周知，EGFR-α6β4促进细胞生长的细胞信号传导。此外，与其他位点相比，位点-11 N-聚糖表现出更多的分支结构，这可能是EGFR-α5β1形成所必需的。综上所述，这些数据清楚地表明，α5上的位点-11 N-糖基化对于其对EGFR信号传导的抑制作用是最重要的，这可能为整合素和EGFR之间的串扰提供了一种新的调节机制。
N-Glycosylation of integrin α5β1 is involved in multiple cell behaviors. We previously reported that the N-glycosylations of the calf domain on integrin α5 (S3–5,10–14) are essential for its inhibitory effect on EGFR signaling in regulating cell proliferation. However, the importance of the individual N-glycosylation and the underlying mechanisms of inhibition remain unclear. Here, we characterize the S3–5,10–14 mutants in detail and found that the N-glycosylation of site-11 (Asn712) is key for cell growth. The restoration of site-11, unlike the other individual sites, significantly suppressed cell growth and EGFR signaling in a manner that was similar to that of wild-type (WT). Mechanistically, this N-glycosylation inhibited the response abilities upon EGF stimulation and EGFR dimerization. Interestingly, we found this N-glycosylation controlled the EGFR complex formation with integrin α5β1 or α6β4; i.e., the loss of site-11 switched EGFR-α5β1 to EGFR-α6β4, which is well known to promote cellular signaling for cell growth. Moreover, the site-11 N-glycan exhibited a more branching structure compared with other sites, which may be required for EGFR-α5β1 formation. Taken together, these data clearly demonstrate that the site-11 N-glycosylation on α5 is most important for its inhibitory effect on EGFR signaling, which may provide a novel regulatory mechanism for crosstalks between integrins and EGFR.
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DOI：
10.1083/jcb.139.1.279
发表时间：
1997-10-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jones PL;Crack J;Rabinovitch M
通讯作者：
Rabinovitch M
影响因子：
3.7
作者：
Kariya Y;Gu J
通讯作者：
Gu J
影响因子：
5.6
作者：
Lambert, Sylviane;Ameels, Helene;Poumay, Yves
通讯作者：
Poumay, Yves
影响因子：
3
作者：
Handa, Kazuko;Hakomori, Sen-itiroh
通讯作者：
Hakomori, Sen-itiroh
影响因子：
3
作者：
Gu, JG;Taniguchi, N
通讯作者：
Taniguchi, N