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Pathway Description
Succinate Signalling During Inflammation
Rattus norvegicus
Category:
Protein Pathway
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Created: 2018-09-14
Last Updated: 2019-08-16
Succinate induces calcium mobilization in an adenylyl cyclase (AC) and protein kinase A (PKA)-dependent manner. Succinate receptor 1 (SUCNR1) engagement activates phospholipase C (PLC), resulting in the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). These second messengers induce calcium mobilization and PKC activation, respectively, and subsequent nitric oxide (NO) and prostaglandin E2 (PGE2) production as well as p38 activation. PKC-dependent phosphorylation of extracellular signal-related kinases ERK1/2 can also drive PG production. SUCNR1 signaling might act in synergy with several inflammatory signaling cascades. PKA is known to phosphorylate and activate the p65 subunit of nuclear factor κB (NF-κB) and cAMP response element-binding protein (CREB). Furthermore, NF-κB, activating protein (AP)-1, nuclear factor of activated T cells (NFAT), and ETS domain-containing protein (Elk-1) are all downstream targets of PKC and MAPKs.
References
Succinate Signalling During Inflammation References
Suh PG, Ryu SH, Moon KH, Suh HW, Rhee SG: Cloning and sequence of multiple forms of phospholipase C. Cell. 1988 Jul 15;54(2):161-9. doi: 10.1016/0092-8674(88)90548-x.
Pubmed: 3390863
Jhon DY, Lee HH, Park D, Lee CW, Lee KH, Yoo OJ, Rhee SG: Cloning, sequencing, purification, and Gq-dependent activation of phospholipase C-beta 3. J Biol Chem. 1993 Mar 25;268(9):6654-61.
Pubmed: 8454637
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.
Pubmed: 22673903
Hamil KG, Hall SH: Cloning of rat Sertoli cell follicle-stimulating hormone primary response complementary deoxyribonucleic acid: regulation of TSC-22 gene expression. Endocrinology. 1994 Mar;134(3):1205-12. doi: 10.1210/endo.134.3.8161377.
Pubmed: 8161377
Nemoto S, DiDonato JA, Lin A: Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase. Mol Cell Biol. 1998 Dec;18(12):7336-43. doi: 10.1128/mcb.18.12.7336.
Pubmed: 9819420
Wooten MW, Geetha T, Seibenhener ML, Babu JR, Diaz-Meco MT, Moscat J: The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination. J Biol Chem. 2005 Oct 21;280(42):35625-9. doi: 10.1074/jbc.C500237200. Epub 2005 Aug 3.
Pubmed: 16079148
Jobin C, Sartor RB: The I kappa B/NF-kappa B system: a key determinant of mucosalinflammation and protection. Am J Physiol Cell Physiol. 2000 Mar;278(3):C451-62. doi: 10.1152/ajpcell.2000.278.3.C451.
Pubmed: 10712233
Saito N, Courtois G, Chiba A, Yamamoto N, Nitta T, Hironaka N, Rowe M, Yamamoto N, Yamaoka S: Two carboxyl-terminal activation regions of Epstein-Barr virus latent membrane protein 1 activate NF-kappaB through distinct signaling pathways in fibroblast cell lines. J Biol Chem. 2003 Nov 21;278(47):46565-75. doi: 10.1074/jbc.M302549200. Epub 2003 Sep 10.
Pubmed: 12968033
Nemeth E, Bole-Feysot C, Tashima LS: Suppression subtractive hybridization (SSH) identifies prolactin stimulation of p38 MAP kinase gene expression in Nb2 T lymphoma cells: molecular cloning of rat p38 MAP kinase. J Mol Endocrinol. 1998 Feb;20(1):151-6.
Pubmed: 9513091
Shi Y, Gaestel M: In the cellular garden of forking paths: how p38 MAPKs signal for downstream assistance. Biol Chem. 2002 Oct;383(10):1519-36. doi: 10.1515/BC.2002.173.
Pubmed: 12452429
Cuadrado A, Nebreda AR: Mechanisms and functions of p38 MAPK signalling. Biochem J. 2010 Aug 1;429(3):403-17. doi: 10.1042/BJ20100323.
Pubmed: 20626350
Saitoh F, Tian QB, Okano A, Sakagami H, Kondo H, Suzuki T: NIDD, a novel DHHC-containing protein, targets neuronal nitric-oxide synthase (nNOS) to the synaptic membrane through a PDZ-dependent interaction and regulates nNOS activity. J Biol Chem. 2004 Jul 9;279(28):29461-8. doi: 10.1074/jbc.M401471200. Epub 2004 Apr 22.
Pubmed: 15105416
Shi Y, Hutchins W, Ogawa H, Chang CC, Pritchard KA Jr, Zhang C, Khampang P, Lazar J, Jacob HJ, Rafiee P, Baker JE: Increased resistance to myocardial ischemia in the Brown Norway vs. Dahl S rat: role of nitric oxide synthase and Hsp90. J Mol Cell Cardiol. 2005 Apr;38(4):625-35. doi: 10.1016/j.yjmcc.2005.02.005.
Pubmed: 15808839
Mohaupt MG, Elzie JL, Ahn KY, Clapp WL, Wilcox CS, Kone BC: Differential expression and induction of mRNAs encoding two inducible nitric oxide synthases in rat kidney. Kidney Int. 1994 Sep;46(3):653-65. doi: 10.1038/ki.1994.318.
Pubmed: 7527874
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0084634
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