BioPAX pathway converted from "Advanced glycosylation endproduct receptor signaling" in the Reactome database. Advanced glycosylation endproduct receptor signaling Advanced glycosylation endproduct receptor signaling This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> The TRTK-12 fragment of F-actin capping protein alpha binds the AGER ligand S100B The TRTK-12 fragment of F-actin capping protein alpha binds the AGER ligand S100B This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 9764031 1 extracellular region GO 0005576 S100B homodimer [extracellular region] S100B homodimer Reactome DB_ID: 9764029 2 UniProt:P50114 S100b Reactome http://www.reactome.org Mus musculus NCBI Taxonomy 10090 UniProt P50114 Chain Coordinates 2 EQUAL 92 EQUAL Reactome Database ID Release 78 9764031 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9764031 Reactome R-MMU-879449 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-879449.1 Converted from EntitySet in Reactome Reactome DB_ID: 9787782 1 F-actin capping protein alpha protein fragment TRTK-12 [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Capza2 [extracellular region] Capza1 [extracellular region] UniProt P47754 UniProt P47753 Reactome DB_ID: 9787784 1 F-actin capping protein fragment TRTK12:S100B homodimer [extracellular region] F-actin capping protein fragment TRTK12:S100B homodimer Reactome DB_ID: 9764031 1 Converted from EntitySet in Reactome Reactome DB_ID: 9787782 1 Reactome Database ID Release 78 9787784 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9787784 Reactome R-MMU-879368 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-879368.1 Reactome Database ID Release 78 9787786 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9787786 Reactome R-MMU-879377 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-879377.1 The TRTK-12 fragment of the F-actin capping protein alpha subunit binds S100B in a calcium dependent manner. S100B undergoes a conformational change that is required for subsequent binding to effector proteins (Inman et al. 2002). S100B is a ligand for AGER (Hofmann et al. 1999). In addition this interaction between S100B andF-actin capping protein alpha could be important for regulating actin filament extension (Ivenkov et al. 1995). 10399917 Pubmed 1999 RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides Hofmann, MA Drury, S Fu, C Qu, W Taguchi, A Lu, Y Avila, C Kambham, N Bierhaus, A Nawroth, P Neurath, MF Slattery, T Beach, D McClary, J Nagashima, M Morser, J Stern, D Schmidt, AM Cell 97:889-901 7540176 Pubmed 1995 Characterization of S-100b binding epitopes. Identification of a novel target, the actin capping protein, CapZ Ivanenkov, VV Jamieson GA, Jr Gruenstein, E Dimlich, RV J Biol Chem 270:14651-8 12470955 Pubmed 2002 Solution NMR structure of S100B bound to the high-affinity target peptide TRTK-12 Inman, KG Yang, R Rustandi, RR Miller, KE Baldisseri, DM Weber, DJ J Mol Biol 324:1003-14 inferred by electronic annotation IEA GO IEA Advanced glycosylation end product-specific receptor (AGER/RAGE) is a multiligand receptor Advanced glycosylation end product-specific receptor (AGER/RAGE) is a multiligand receptor This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 9764043 1 AGER ligands [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Hmgb1 [extracellular region] App [extracellular region] UniProt P63158 UniProt P12023 Reactome DB_ID: 9764025 1 plasma membrane GO 0005886 UniProt:Q62151 Ager UniProt Q62151 23 EQUAL 404 EQUAL Reactome DB_ID: 9764045 1 AGER ligands:AGER [plasma membrane] AGER ligands:AGER Converted from EntitySet in Reactome Reactome DB_ID: 9764043 1 Reactome DB_ID: 9764025 1 23 EQUAL 404 EQUAL Reactome Database ID Release 78 9764045 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9764045 Reactome R-MMU-879365 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-879365.1 Reactome Database ID Release 78 9787788 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9787788 Reactome R-MMU-879411 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-879411.1 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 recognizes a large variety of modified proteins known as advanced glycation/glycosylation endproducts (AGEs) a heterogenous group of structures (Ikeda et al. 1996) that accumulate in patients with diabetes, atherosclerosis, renal failure or ageing (Schmidt et al. 1999). The most prevalent class of AGE in vivo are N(6)-carboxymethyllysine (NECML) adducts (Kislinger et al. 1991). AGER is a receptor for amyloid-beta peptide (Ab)(Yan et al. 1996), mediating Ab neurotoxicity and promoting Ab influx into the brain (Zhang et al. 2009). AGER also responds to the proinflammatory S100/calgranulins (Hofmann et al. 1999) and High mobility group protein B1 (HMGB1/Amphoterin/DEF) (Hori et al. 1995). The major pathway is NFkappaB activation, but AGER can also activate rho-GTPases and thereby MAPK and JNK cascades. (Bierhaus et al. 2005). 8672512 Pubmed 1996 N (epsilon)-(carboxymethyl)lysine protein adduct is a major immunological epitope in proteins modified with advanced glycation end products of the Maillard reaction Ikeda, K Higashi, T Sano, H Jinnouchi, Y Yoshida, M Araki, T Ueda, S Horiuchi, S Biochemistry 35:8075-83 7592757 Pubmed 1995 The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system Hori, O Brett, J Slattery, T Cao, R Zhang, J Chen, JX Nagashima, M Lundh, ER Vijay, S Nitecki, D J Biol Chem 270:25752-61 16133426 Pubmed 2005 Understanding RAGE, the receptor for advanced glycation end products Bierhaus, A Humpert, PM Morcos, M Wendt, T Chavakis, T Arnold, B Stern, DM Nawroth, PP J Mol Med 83:876-86 8751438 Pubmed 1996 RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease Yan, SD Chen, X Fu, J Chen, M Zhu, H Roher, A Slattery, T Zhao, L Nagashima, M Morser, J Migheli, A Nawroth, P Stern, D Schmidt, AM Nature 382:685-91 19672558 Pubmed 2009 Ectodomain shedding of the receptor for advanced glycation end products: a novel therapeutic target for Alzheimer's disease Zhang, L Postina, R Wang, Y Cell Mol Life Sci 66:3923-35 10531386 Pubmed 1999 N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression Kislinger, T Fu, C Huber, B Qu, W Taguchi, A Du Yan, S Hofmann, M Yan, SF Pischetsrieder, M Stern, D Schmidt, AM J Biol Chem 274:31740-9 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 78 9861970 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9861970 Reactome R-MMU-879415 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-879415.1 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). 11723063 Pubmed 2001 Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB Bierhaus, A Schiekofer, S Schwaninger, M Andrassy, M Humpert, PM Chen, J Hong, M Luther, T Henle, T Klöting, I Morcos, M Hofmann, M Tritschler, H Weigle, B Kasper, M Smith, M Perry, George Schmidt, AM Stern, DM Häring, Hans-Ulrich Schleicher, E Nawroth, PP Diabetes 50:2792-808 15173891 Pubmed 2004 Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response Liliensiek, B Weigand, MA Bierhaus, A Nicklas, W Kasper, M Hofer, S Plachky, J Gröne, HJ Kurschus, FC Schmidt, AM Yan, SD Martin, E Schleicher, E Stern, DM Hämmerling G, G Nawroth, PP Arnold, B J Clin Invest 113:1641-50 inferred by electronic annotation IEA GO IEA