KEGG   PATHWAY: rno04657
Entry
rno04657                    Pathway                                

Name
IL-17 signaling pathway - Rattus norvegicus (rat)
Description
The interleukin 17 (IL-17) family, a subset of cytokines consisting of IL-17A-F, plays crucial roles in both acute and chronic inflammatory responses. IL-17A, the hallmark cytokine of the newly defined T helper 17 (TH17) cell subset, has important roles in protecting the host against extracellular pathogens, but also promotes inflammatory pathology in autoimmune disease, whereas IL-17F is mainly involved in mucosal host defense mechanisms. IL-17E (IL-25) is an amplifier of Th2 immune responses. IL-17C has biological functions similar to those of IL-17A. The functions of IL-17B and IL-17D remain largely elusive. The IL-17 family signals via their correspondent receptors and activates downstream pathways that include NF-kappaB, MAPKs and C/EBPs to induce the expression of antimicrobial peptides, cytokines and chemokines. The receptor proximal adaptor Act1 (an NF-kappaB activator 1) is considered as the master mediator in IL-17A signaling. It is likely that Act1 is a common signal adaptor also shared by other members mediated signalings in this family.
Class
Organismal Systems; Immune system
Pathway map
rno04657  IL-17 signaling pathway
rno04657

Other DBs
GO: 0097400
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
501996  Il25; interleukin-25 [KO:K05493]
312679  Il17ra; interleukin-17 receptor A [KO:K05164]
306247  Il17rb; interleukin-17 receptor B [KO:K05165]
246756  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
266610  Fadd; FAS-associated death domain protein [KO:K02373]
25402  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
64044  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
361857  Traf3ip2; adapter protein CIKS [KO:K21124]
311245  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
309165  Rela; transcription factor p65 [KO:K04735]
314322  Fos; proto-oncogene c-Fos [KO:K04379]
100360880  Fosb; protein fosB [KO:K09029]
24516  Jun; transcription factor AP-1 [KO:K04448]
24518  Jund; transcription factor jun-D isoform JunD-FL [KO:K04449]
25445  Fosl1; fos-related antigen 1 [KO:K04502]
287287  Il4; interleukin-4 precursor [KO:K05430]
24497  Il5; interleukin-5 precursor [KO:K05428]
116553  Il13; interleukin-13 precursor [KO:K05435]
117518  Ccl17; C-C motif chemokine 17 precursor [KO:K21083]
29397  Ccl11; eotaxin precursor [KO:K16597]
301289  Il17a; interleukin-17A precursor [KO:K05489]
301291  Il17f; interleukin-17F precursor [KO:K05494]
297520  Il17rc; interleukin-17 receptor C precursor [KO:K05166]
362788  Traf3; TNF receptor-associated factor 3 [KO:K03174]
288671  Anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
683206  Tnfaip3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
299331  Hsp90aa1; heat shock protein HSP 90-alpha [KO:K04079]
301252  Hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
362862  Hsp90b1; endoplasmin precursor [KO:K09487]
299827  Tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
308267  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
317546  Tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
313121  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
58840  Mapk6; mitogen-activated protein kinase 6 [KO:K06855] [EC:2.7.11.24]
54268  Mapk4; mitogen-activated protein kinase 4 [KO:K06855] [EC:2.7.11.24]
114509  Mapk7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
286997  Mapk15; mitogen-activated protein kinase 15 [KO:K19603] [EC:2.7.11.24]
24253  Cebpb; CCAAT/enhancer-binding protein beta isoform LAP1 [KO:K10048]
303285  Traf4; TNF receptor-associated factor 4 [KO:K09848]
363984  Ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
304150  Usp25; ubiquitin carboxyl-terminal hydrolase 25 [KO:K11849] [EC:3.4.19.12]
684173  Traf5; TNF receptor-associated factor 5 [KO:K09849]
311786  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
689890  Srsf1; serine/arginine-rich splicing factor 1 [KO:K12890]
363854  Elavl1; ELAV-like protein 1 [KO:K13088]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
81503  Cxcl1; growth-regulated alpha protein precursor [KO:K05505]
114105  Cxcl2; C-X-C motif chemokine 2 precursor [KO:K05505]
171551  Cxcl3; C-X-C motif chemokine 3 precursor [KO:K05505]
60665  Cxcl6; C-X-C motif chemokine 5 precursor [KO:K05506]
245920  Cxcl10; C-X-C motif chemokine 10 precursor [KO:K12671]
287562  Ccl12; chemokine (C-C motif) ligand 12 precursor [KO:K14624]
24770  Ccl2; C-C motif chemokine 2 precursor [KO:K14624]
287561  Ccl7; C-C motif chemokine 7 precursor [KO:K05509]
29538  Ccl20; C-C motif chemokine 20 precursor [KO:K14625]
24498  Il6; interleukin-6 precursor [KO:K05405]
24835  Tnf; tumor necrosis factor [KO:K03156]
29527  Ptgs2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]
25610  Csf3; granulocyte colony-stimulating factor precursor [KO:K05423]
116630  Csf2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
64389  Defb4; beta-defensin 4 precursor [KO:K21100]
682837  Muc5ac; mucin-5AC [KO:K21125]
309114  Muc5b; mucin-5B [KO:K13908]
116547  S100a8; protein S100-A8 [KO:K21127]
94195  S100a9; protein S100-A9 [KO:K21128]
170496  Lcn2; neutrophil gelatinase-associated lipocalin precursor [KO:K21129]
300339  Mmp1; interstitial collagenase precursor [KO:K01388] [EC:3.4.24.7]
300338  Mmp1b; interstitial collagenase B [KO:K01388] [EC:3.4.24.7]
171045  Mmp3; stromelysin-1 preproprotein [KO:K01394] [EC:3.4.24.17]
81687  Mmp9; matrix metalloproteinase-9 precursor [KO:K01403] [EC:3.4.24.35]
171052  Mmp13; collagenase 3 precursor [KO:K07994] [EC:3.4.24.-]
691516  Il17c; interleukin-17C precursor [KO:K05491]
362417  Il17re; interleukin-17 receptor E precursor [KO:K05168]
24494  Il1b; interleukin-1 beta [KO:K04519]
25712  Ifng; interferon gamma precursor [KO:K04687]
116472  Il17b; interleukin-17B precursor [KO:K05490]
691799  Il17d; collagen alpha-1(I) chain [KO:K05492]
Reference
  Authors
Song X, Qian Y
  Title
IL-17 family cytokines mediated signaling in the pathogenesis of inflammatory diseases.
  Journal
Cell Signal 25:2335-47 (2013)
DOI:10.1016/j.cellsig.2013.07.021
Reference
  Authors
Song X, Qian Y
  Title
The activation and regulation of IL-17 receptor mediated signaling.
  Journal
Cytokine 62:175-82 (2013)
DOI:10.1016/j.cyto.2013.03.014
Reference
  Authors
Gu C, Wu L, Li X
  Title
IL-17 family: cytokines, receptors and signaling.
  Journal
Cytokine 64:477-85 (2013)
DOI:10.1016/j.cyto.2013.07.022
Reference
  Authors
Gaffen SL, Jain R, Garg AV, Cua DJ
  Title
The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing.
  Journal
Nat Rev Immunol 14:585-600 (2014)
DOI:10.1038/nri3707
Reference
  Authors
Iwakura Y, Ishigame H, Saijo S, Nakae S
  Title
Functional specialization of interleukin-17 family members.
  Journal
Immunity 34:149-62 (2011)
DOI:10.1016/j.immuni.2011.02.012
Reference
  Authors
Qian Y, Kang Z, Liu C, Li X
  Title
IL-17 signaling in host defense and inflammatory diseases.
  Journal
Cell Mol Immunol 7:328-33 (2010)
DOI:10.1038/cmi.2010.27
Reference
  Authors
Zhu S, Qian Y
  Title
IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential.
  Journal
Clin Sci (Lond) 122:487-511 (2012)
DOI:10.1042/CS20110496
Reference
  Authors
Zenobia C, Hajishengallis G
  Title
Basic biology and role of interleukin-17 in immunity and inflammation.
  Journal
Periodontol 2000 69:142-59 (2015)
DOI:10.1111/prd.12083
Reference
  Authors
Reynolds JM, Angkasekwinai P, Dong C
  Title
IL-17 family member cytokines: regulation and function in innate immunity.
  Journal
Cytokine Growth Factor Rev 21:413-23 (2010)
DOI:10.1016/j.cytogfr.2010.10.002
Reference
  Authors
Gaffen SL
  Title
Recent advances in the IL-17 cytokine family.
  Journal
Curr Opin Immunol 23:613-9 (2011)
DOI:10.1016/j.coi.2011.07.006
Reference
  Authors
Gaffen SL
  Title
An overview of IL-17 function and signaling.
  Journal
Cytokine 43:402-7 (2008)
DOI:10.1016/j.cyto.2008.07.017
Reference
  Authors
Hu Y, Shen F, Crellin NK, Ouyang W
  Title
The IL-17 pathway as a major therapeutic target in autoimmune diseases.
  Journal
Ann N Y Acad Sci 1217:60-76 (2011)
DOI:10.1111/j.1749-6632.2010.05825.x
Reference
  Authors
Xu S, Cao X
  Title
Interleukin-17 and its expanding biological functions.
  Journal
Cell Mol Immunol 7:164-74 (2010)
DOI:10.1038/cmi.2010.21
Reference
  Authors
Pappu R, Ramirez-Carrozzi V, Ota N, Ouyang W, Hu Y
  Title
The IL-17 family cytokines in immunity and disease.
  Journal
J Clin Immunol 30:185-95 (2010)
DOI:10.1007/s10875-010-9369-6
Reference
  Authors
Gaffen SL
  Title
Structure and signalling in the IL-17 receptor family.
  Journal
Nat Rev Immunol 9:556-67 (2009)
DOI:10.1038/nri2586
Reference
  Authors
Shen F, Gaffen SL
  Title
Structure-function relationships in the IL-17 receptor: implications for signal transduction and therapy.
  Journal
Cytokine 41:92-104 (2008)
DOI:10.1016/j.cyto.2007.11.013
Reference
  Authors
Doyle MS, Collins ES, FitzGerald OM, Pennington SR
  Title
New insight into the functions of the interleukin-17 receptor adaptor protein Act1 in psoriatic arthritis.
  Journal
Arthritis Res Ther 14:226 (2012)
DOI:10.1186/ar4071
Reference
  Authors
Gaffen SL, Kramer JM, Yu JJ, Shen F
  Title
The IL-17 cytokine family.
  Journal
Vitam Horm 74:255-82 (2006)
DOI:10.1016/S0083-6729(06)74010-9
Reference
  Authors
Chang SH, Dong C
  Title
Signaling of interleukin-17 family cytokines in immunity and inflammation.
  Journal
Cell Signal 23:1069-75 (2011)
DOI:10.1016/j.cellsig.2010.11.022
Reference
  Authors
Cortez DM, Feldman MD, Mummidi S, Valente AJ, Steffensen B, Vincenti M, Barnes JL, Chandrasekar B
  Title
IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-beta , NF-kappaB, and AP-1 activation.
  Journal
Am J Physiol Heart Circ Physiol 293:H3356-65 (2007)
DOI:10.1152/ajpheart.00928.2007
Reference
  Authors
Qu F, Gao H, Zhu S, Shi P, Zhang Y, Liu Y, Jallal B, Yao Y, Shi Y, Qian Y
  Title
TRAF6-dependent Act1 phosphorylation by the IkappaB kinase-related kinases suppresses interleukin-17-induced NF-kappaB activation.
  Journal
Mol Cell Biol 32:3925-37 (2012)
DOI:10.1128/MCB.00268-12
Reference
  Authors
Sharkhuu T, Matthaei KI, Forbes E, Mahalingam S, Hogan SP, Hansbro PM, Foster PS
  Title
Mechanism of interleukin-25 (IL-17E)-induced pulmonary inflammation and airways hyper-reactivity.
  Journal
Clin Exp Allergy 36:1575-83 (2006)
DOI:10.1111/j.1365-2222.2006.02595.x
Related
pathway
rno04010  MAPK signaling pathway
rno04060  Cytokine-cytokine receptor interaction
rno04064  NF-kappa B signaling pathway
rno04210  Apoptosis
rno04659  Th17 cell differentiation
KO pathway
ko04657   

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