Homodimerization is essential for the receptor for advanced glycation end products (RAGE)-mediated signal transduction

Zong, Hongliang, Madden, Angelina, Ward, Micheal, Mooney, Mark H., Elliott, Christopher T. and Stitt, Alan W. (2010) Homodimerization is essential for the receptor for advanced glycation end products (RAGE)-mediated signal transduction. Journal of Biological Chemistry, 285 30: 23137-23146. doi:10.1074/jbc.M110.133827

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Author Zong, Hongliang
Madden, Angelina
Ward, Micheal
Mooney, Mark H.
Elliott, Christopher T.
Stitt, Alan W.
Title Homodimerization is essential for the receptor for advanced glycation end products (RAGE)-mediated signal transduction
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2010-07
Sub-type Article (original research)
DOI 10.1074/jbc.M110.133827
Open Access Status File (Publisher version)
Volume 285
Issue 30
Start page 23137
End page 23146
Total pages 10
Place of publication Bethesda, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject 1307 Cell Biology
1312 Molecular Biology
Abstract The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor that binds to diverse ligands and initiates a downstream proinflammatory signaling cascade. RAGE activation has been linked to diabetic complications, Alzheimer disease, infections, and cancers. RAGE is known to mediate cell signaling and downstream proinflammatory gene transcription activation, although the precise mechanism surrounding receptor-ligand interactions is still being elucidated. Recent fluorescence resonance energy transfer evidence indicates that RAGE may form oligomers on the cell surface and that this could be related to signal transduction. To investigate whether RAGE forms oligomers, protein-protein interaction assays were carried out. Here, we demonstrate the interaction between RAGE molecules via their N-terminal V domain, which is an important region involved in ligand recognition. By protein cross-linking using water-soluble and membrane-impermeable cross-linker bis(sulfosuccinimidyl) suberate and nondenaturing gels, we show that RAGE forms homodimers at the plasma membrane, a process potentiated by S100B and advanced glycation end products. Soluble RAGE, the RAGE inhibitor, is also capable of binding to RAGE, similar to V peptide, as shown by surface plasmon resonance. Incubation of cells with soluble RAGE or RAGE V domain peptide inhibits RAGE dimerization, subsequent phosphorylation of intracellular MAPK proteins, and activation of NF-κB pathways. Thus, the data indicate that dimerization of RAGE represents an important component of RAGE-mediated cell signaling.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
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