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Pathway Description
NF-kB Signaling Pathway
Rattus norvegicus
Category:
Protein Pathway
Sub-Categories:
Stress-Activated Signaling
Pathogen-Activated Signaling
Gene Regulatory
Kinase Signaling
Immunological
Cellular Response
Created: 2018-09-20
Last Updated: 2019-09-15
NF-κB can be found in almost all animal cells. NF-κB is crucial for cell growth since it can control cytokine production, DNA transcription, as well as cell survival. NF-κB can also respond to stress, free radicals, and UV irradiation. It can also respond to bacterial and viral antigens; therefore, it plays an important role in the immune response of infections. Various diseases such as cancer and immune diseases (and more) can be related to the incorrect regulation of the NF-κB complex. The activation of NF-κB involves two major signalling pathways: the canonical pathways, which responds to diverse stimuli such as ligands of various cytokine receptors, pattern-recognition receptors (PRRs), and the noncanonical (or alternative) pathway, which selectively responds to a specific group of stimuli, such as groups of ligands of a subset of TNFR superfamily members (e.g. LTβR, BAFFR, CD40 and RANK). Both pathways are important for regulating immune and inflammatory responses despite their differences in signalling mechanism.
References
NF-kB Signaling Pathway References
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F: Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004 Apr 1;428(6982):493-521. doi: 10.1038/nature02426.
Pubmed: 15057822
Florea L, Di Francesco V, Miller J, Turner R, Yao A, Harris M, Walenz B, Mobarry C, Merkulov GV, Charlab R, Dew I, Deng Z, Istrail S, Li P, Sutton G: Gene and alternative splicing annotation with AIR. Genome Res. 2005 Jan;15(1):54-66. doi: 10.1101/gr.2889405.
Pubmed: 15632090
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
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
Xu S, Robbins DJ, Christerson LB, English JM, Vanderbilt CA, Cobb MH: Cloning of rat MEK kinase 1 cDNA reveals an endogenous membrane-associated 195-kDa protein with a large regulatory domain. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5291-5. doi: 10.1073/pnas.93.11.5291.
Pubmed: 8643568
Chadee DN, Yuasa T, Kyriakis JM: Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2. Mol Cell Biol. 2002 Feb;22(3):737-49. doi: 10.1128/mcb.22.3.737-749.2002.
Pubmed: 11784851
Ye B, Yu WP, Thomas GM, Huganir RL: GRASP-1 is a neuronal scaffold protein for the JNK signaling pathway. FEBS Lett. 2007 Sep 18;581(23):4403-10. doi: 10.1016/j.febslet.2007.08.008. Epub 2007 Aug 14.
Pubmed: 17761173
Patriotis C, Makris A, Bear SE, Tsichlis PN: Tumor progression locus 2 (Tpl-2) encodes a protein kinase involved in the progression of rodent T-cell lymphomas and in T-cell activation. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2251-5. doi: 10.1073/pnas.90.6.2251.
Pubmed: 7681591
Belich MP, Salmeron A, Johnston LH, Ley SC: TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105. Nature. 1999 Jan 28;397(6717):363-8. doi: 10.1038/16946.
Pubmed: 9950430
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
Frantz S, Kobzik L, Kim YD, Fukazawa R, Medzhitov R, Lee RT, Kelly RA: Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest. 1999 Aug;104(3):271-80. doi: 10.1172/JCI6709.
Pubmed: 10430608
Himmler A, Maurer-Fogy I, Kronke M, Scheurich P, Pfizenmaier K, Lantz M, Olsson I, Hauptmann R, Stratowa C, Adolf GR: Molecular cloning and expression of human and rat tumor necrosis factor receptor chain (p60) and its soluble derivative, tumor necrosis factor-binding protein. DNA Cell Biol. 1990 Dec;9(10):705-15. doi: 10.1089/dna.1990.9.705.
Pubmed: 1702293
Furuya T, Salstrom JL, Joe B, Hashiramoto A, Dobbins DE, Wilder RL, Remmers EF: Polymorphisms of the tumor necrosis factor receptor type 1 locus among autoimmune susceptible and resistant inbred rat strains. Immunogenetics. 2001 Jul;53(5):427-9.
Pubmed: 11486281
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 SMP0063813
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