Receptor for advanced glycosylation end products (RAGE)
Receptor for Advanced Glycosylation End products (RAGE) is a 35kD transmembrane receptor in the immunoglobulin super family. The interaction between RAGE and its ligands results in pro-inflammatory gene activation. Isoforms of the RAGE protein, which lack the transmembrane and the signalling domain, are referred to as soluble RAGE or sRAGE. They are believed to counteract the pro-inflammatory actions of the RAGE receptor. RAGE mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and, at an accelerated rate, in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100 A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. RAGE is also a receptor for amyloid beta peptide. It contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space.
Swiss-Prot Accession Number: Q15109