Identification of the minimal N-glycosylation on integrin α5β1 required for its inhibitory effect on EGFR signaling and cell proliferation
Identification of the minimal N-glycosylation on integrin α5β1 required for its inhibitory effect on EGFR signaling and cell proliferation
复制标题
鉴定整合素 α 5 β 1 上的最小 N-糖基化，以实现其对 EGFR 信号传导和细胞增殖的抑制作用
DOI：
10.1016/j.bbrc.2019.11.188
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发表时间：
2020-02-26
影响因子：
3.1
通讯作者：
Gu, Jianguo
中科院分区：
文献类型：
--
作者：
Hou, Sicong;Hang, Qinglei;Gu, Jianguo
整合素α 5 β 1的N-糖基化参与多种细胞生物学功能。本课题组先前报道了α 5亚基（S3- 5，10 -14）上Calf-1，2结构域的N-糖基化对于其通过调节α 5-EGFR复合物的形成对EGFR信号传导的抑制作用是重要的。在这项后续研究中，我们提供的证据表明，整合素β 1亚基上的N-糖基化通过促进其与EGFR在纤连蛋白（FN）包被条件下的结合来抑制细胞生长。野生型（WT）β 1的表达，而不是N-糖基化突变体S4-6 β 1，其含有较少的N-聚糖，抑制EGFR信号传导和细胞粘附到FN后的细胞增殖。此外，β 1位点1-3上N-聚糖的一致恢复恢复了抑制作用。在机制上，131的N-糖基化突变体（S4-6+1-3）通过促进α 5 β 1-EGFR复合物的形成来抑制EGF刺激后的EGFR应答。此外，我们鉴定了α 5上位点10-14和β 1上位点1-3的N-糖基化对EGFR信号传导最重要。总之，这些数据表明α 5（S3-5+10-14）β 1（S4-6+1-3）突变体代表其调节EGFR信号传导和细胞增殖所需的最小N-糖基化，为α 5 β 1和EGFR之间的串扰提供了合理的机制。(C)2019爱思唯尔公司All rights reserved.
The N-glycosylation of integrin alpha 5 beta 1 is involved in multiple cell biological functions. Our group previously reported that the N-glycosylation of the Calf-1,2 domain on alpha 5 subunit (S3-5,10-14) was important for its inhibitory effect on EGFR signaling through regulating alpha 5-EGFR complex formation. In this followup study, we provide evidence that the N-glycosylation on integrin beta 1 subunit suppress cell growth by promoting its association with EGFR under fibronectin (FN)-coated conditions. Expression of wild-type (WT) beta 1, but not the N-glycosylation mutant S4-6 beta 1, which contains fewer N-glycans, inhibited EGFR signaling and cell proliferation after cell adhesion to FN. Furthermore, consistent restoration of the N-glycans on sites 1-3 of beta 1 reinstated the inhibitory effects. Mechanistically, the N-glycosylation mutant of 131 (S4-6+1-3) inhibited the EGFR response upon EGF stimulation via facilitating the alpha 5 beta 1-EGFR complex formation. Moreover, we identified the N-glycosylation of sites 10-14 on alpha 5 and 1-3 on beta 1 were most - important for EGFR signaling. Taken together, these data indicate that alpha 5(S3-5+10-14)beta 1(S4-6+1-3) mutant represents the minimal N-glycosylation required for its regulation on EGFR signaling and cell prolifer ation, providing a plausible mechanism for the crosstalk between with alpha 5 beta 1 and EGFR. (C) 2019 Elsevier Inc. All rights reserved.