期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep33507
关键词
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资金
- Japan Society for the Promotion of Science [15H04354, 24570169, 15K14408]
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Grants-in-Aid for Scientific Research [15H04354, 25461164, 24570169, 15K14408] Funding Source: KAKEN
N-Glycosylation of integrin alpha 5 beta 1 is involved in multiple cell behaviors. We previously reported that the N-glycosylations of the calf domain on integrin alpha 5 (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 alpha 5 beta 1 or alpha 6 beta 4; i.e., the loss of site-11 switched EGFR-alpha 5 beta 1 to EGFR-alpha 6 beta 4, 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-alpha 5 beta 1 formation. Taken together, these data clearly demonstrate that the site-11 N-glycosylation on a5 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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