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Calcium-Binding Proteins and RAGE

Volume 963 of the series Methods in Molecular Biology pp 239-263

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RAGE-Mediated Cell Signaling

  • Ari RouhiainenAffiliated withNeuroscience Center, University of Helsinki Email author 
  • , Juha Kuja-PanulaAffiliated withNeuroscience Center, University of Helsinki
  • , Sarka TumovaAffiliated withFaculty of Biological Sciences, Multidisciplinary Cardiovascular Research Center and the Institute of Membrane & Systems Biology, University of Leeds
  • , Heikki RauvalaAffiliated withNeuroscience Center, University of Helsinki

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Abstract

RAGE (receptor for advanced glycation end products) is a multi-ligand receptor that belongs to the immunoglobulin superfamily of transmembrane proteins. RAGE binds AGEs (advanced glycation end products), HMGB1 (high-mobility group box-1; also designated as amphoterin), members of the S100 protein family, glycosaminoglycans and amyloid β peptides. Recent studies using tools of structural biology have started to unravel common molecular patterns in the diverse set of ligands recognized by RAGE. The distal Ig domain (V1 domain) of RAGE has a positively charged patch, the geometry of which fits to anionic surfaces displayed at least in a proportion of RAGE ligands. Association of RAGE to itself, to HSPGs (heparan sulfate proteoglycans), and to Toll-like receptors in the cell membrane plays a key role in cell signaling initiated by RAGE ligation. Ligation of RAGE activates cell signaling pathways that regulate migration of several cell types. Furthermore, RAGE ligation has profound effects on the transcriptional profile of cells. RAGE signaling has been mainly studied as a pathogenetic factor of several diseases, where acute or chronic inflammation plays a role. Recent studies have suggested a physiological role for RAGE in normal lung function and in neuronal signaling.

Key words

RAGE HSPG Heparin Toll-like receptors AGE HMGB1 Amphoterin S100 proteins EF-hand Calcium β amyloid Inflammation