論文 - 詳細
| RRC ID | 51863 |
|---|---|
| 著者 | Hang Q, Isaji T, Hou S, Zhou Y, Fukuda T, Gu J. |
| タイトル | N-Glycosylation of integrin α5 acts as a switch for EGFR-mediated complex formation of integrin α5β1 to α6β4. |
| ジャーナル | Sci Rep |
| Abstract |
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. |
| 巻・号 | 6 |
| ページ | 33507 |
| 公開日 | 2016-9-19 |
| DOI | 10.1038/srep33507 |
| PII | srep33507 |
| PMID | 27641064 |
| PMC | PMC5027594 |
| MeSH | Animals CHO Cells Cell Proliferation Cricetinae Cricetulus Epidermal Growth Factor / pharmacology ErbB Receptors / metabolism* Glycosylation HeLa Cells Humans Integrin alpha5 / chemistry Integrin alpha5 / metabolism* Integrin alpha5beta1 / metabolism* Integrin alpha6beta4 / metabolism* Models, Biological Mutant Proteins / chemistry Mutant Proteins / metabolism Polysaccharides / chemistry Polysaccharides / metabolism Protein Domains Protein Multimerization Protein Subunits / chemistry Protein Subunits / metabolism Signal Transduction |
| IF | 3.998 |
| 引用数 | 14 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) HeLa |