AGER-1,2,3 bind AGEs AGER binds ERK1/2 Advanced glycosylation end product-specific receptor (AGER/RAGE) is a multiligand receptor The TRTK-12 fragment of F-actin capping protein alpha binds the AGER ligand S100B PathwayStep6918 PathwayStep6917 PathwayStep6916 PathwayStep6915 Advanced glycosylation endproduct receptor signaling Advanced Glycosylation End- product-specific Receptor (AGER) also known as Receptor for Advanced Glycation End-products (RAGE) is a multi-ligand membrane receptor belonging to the immunoglobulin superfamily. It is considered to be a Pattern Recognition Receptor (Liliensiek et al. 2004). It recognizes a large variety of modified proteins known as advanced glycation/glycosylation endproducts (AGEs), a heterogenous group of structures that are generated by the Maillard reaction, a consequence of long-term incubation of proteins with glucose (Ikeda et al. 1996). Their accumulation is associated with diabetes, atherosclerosis, renal failure and ageing (Schmidt et al. 1999). The most prevalent class of AGE in vivo are N(6)-carboxymethyllysine (NECML) adducts (Kislinger et al. 1991). In addition to AGEs, AGER is a signal transduction receptor for amyloid-beta peptide (Ab) (Yan et al. 1996), mediating Ab neurotoxicity and promoting Ab influx into the brain. AGER also responds to the proinflammatory S100/calgranulins (Hofmann et al. 1999) and High mobility group protein B1 (HMGB1/Amphoterin/DEF), a protein linked to neurite outgrowth and cellular motility (Hori et al. 1995).<br><br>The major inflammatory pathway stimulated by AGER activation is NFkappaB. Though the signaling cascade is unclear, several pieces of experimental data suggest that activation of AGER leads to sustained activation and upregulation of NFkappaB, measured as NFkappaB translocation to the nucleus, and increased levels of de novo synthesized NFkappaB (Bierhaus et al. 2001). As this is clearly an indirect effect it is represented here as positive regulation of NFkappaB translocation to the nucleus. AGER can bind ERK1/2 and thereby activate the MAPK and JNK cascades (Bierhaus et al. 2005). Authored: Jupe, S, 2010-06-01 Edited: Jupe, S, 2010-09-01 Pubmed10399917 Pubmed10531386 Pubmed11723063 Pubmed15173891 Pubmed16133426 Pubmed7592757 Pubmed8672512 Pubmed8751438 Reactome Database ID Release 43879415 Reactome, http://www.reactome.org ReactomeREACT_25195 Reviewed: Yan, SD, 2010-11-09