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| Content Provider | PubMed Central |
|---|---|
| Author | Park, Sun Jin Kleffmann, Torsten Hessian, Paul A. |
| Copyright Year | 2011 |
| Abstract | Interaction between the receptor for advanced glycation end products (RAGE) and its ligands amplifies the proinflammatory response. N-Linked glycosylation of RAGE plays an important role in the regulation of ligand binding. Two potential sites for N-linked glycosylation, at Asn25 and Asn81, are implicated, one of which is potentially influenced by a naturally occurring polymorphism that substitutes Gly82 with Ser. This G82S polymorphic RAGE variant displays increased ligand binding and downstream signaling. We hypothesized that the G82S polymorphism affects RAGE glycosylation and thereby affects ligand binding. WT or various mutant forms of RAGE protein, including N25Q, N81Q, N25Q/G82S, and N25Q/N81Q, were produced by transfecting HEK293 cells. The glycosylation patterns of expressed proteins were compared. Enzymatic deglycosylation showed that WT RAGE and the G82S polymorphic variant are glycosylated to the same extent. Our data also revealed N-linked glycosylation of N25Q and N81Q mutants, suggesting that both Asn25 and Asn81 can be utilized for N-linked glycosylation. Using mass spectrometry analysis, we found that Asn81 may or may not be glycosylated in WT RAGE, whereas in G82S RAGE, Asn81 is always glycosylated. Furthermore, RAGE binding to S100B ligand is affected by Asn81 glycosylation, with consequences for NF-κB activation. Therefore, the G82S polymorphism promotes N-linked glycosylation of Asn81, which has implications for the structure of the ligand binding region of RAGE and might explain the enhanced function associated with the G82S polymorphic RAGE variant. |
| Related Links | http://dx.doi.org/10.1074/jbc.m111.241281 |
| Ending Page | 21392 |
| Page Count | 9 |
| Starting Page | 21384 |
| File Format | |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | The Journal of Biological Chemistry |
| Issue Number | 24 |
| Volume Number | 286 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2011-06-17 |
| Access Restriction | Open |
| Rights Holder | American Society for Biochemistry and Molecular Biology |
| Subject Keyword | Cell Biology Biochemistry Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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