KEGG   PATHWAY: mmu04657
Entry
mmu04657                    Pathway                                
Name
IL-17 signaling pathway - Mus musculus (house mouse)
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
mmu04657  IL-17 signaling pathway
mmu04657

Other DBs
GO: 0097400
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
140806  Il25; interleukin 25 [KO:K05493]
16172  Il17ra; interleukin 17 receptor A [KO:K05164]
50905  Il17rb; interleukin 17 receptor B [KO:K05165]
71609  Tradd; TNFRSF1A-associated via death domain [KO:K03171]
14082  Fadd; Fas associated via death domain [KO:K02373]
12367  Casp3; caspase 3 [KO:K02187] [EC:3.4.22.56]
12370  Casp8; caspase 8 [KO:K04398] [EC:3.4.22.61]
103213  Traf3ip2; TRAF3 interacting protein 2 [KO:K21124]
22034  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
14281  Fos; FBJ osteosarcoma oncogene [KO:K04379]
14282  Fosb; FBJ osteosarcoma oncogene B [KO:K09029]
16476  Jun; jun proto-oncogene [KO:K04448]
16478  Jund; jun D proto-oncogene [KO:K04449]
14283  Fosl1; fos-like antigen 1 [KO:K04502]
16189  Il4; interleukin 4 [KO:K05430]
16191  Il5; interleukin 5 [KO:K05428]
16163  Il13; interleukin 13 [KO:K05435]
20295  Ccl17; C-C motif chemokine ligand 17 [KO:K21083]
20292  Ccl11; C-C motif chemokine ligand 11 [KO:K16597]
16171  Il17a; interleukin 17A [KO:K05489]
257630  Il17f; interleukin 17F [KO:K05494]
171095  Il17rc; interleukin 17 receptor C [KO:K05166]
22031  Traf3; TNF receptor-associated factor 3 [KO:K03174]
59008  Anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
21929  Tnfaip3; tumor necrosis factor, alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
15519  Hsp90aa1; heat shock protein 90, alpha (cytosolic), class A member 1 [KO:K04079]
15516  Hsp90ab1; heat shock protein 90 alpha (cytosolic), class B member 1 [KO:K04079]
22027  Hsp90b1; heat shock protein 90, beta (Grp94), member 1 [KO:K09487]
56480  Tbk1; TANK-binding kinase 1 [KO:K05410] [EC:2.7.11.10]
68652  Tab2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
66724  Tab3; TGF-beta activated kinase 1/MAP3K7 binding protein 3 [KO:K12793]
26409  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
16151  Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
12675  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
225724  Mapk4; mitogen-activated protein kinase 4 [KO:K06855] [EC:2.7.11.24]
50772  Mapk6; mitogen-activated protein kinase 6 [KO:K06855] [EC:2.7.11.24]
23939  Mapk7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
332110  Mapk15; mitogen-activated protein kinase 15 [KO:K19603] [EC:2.7.11.24]
12608  Cebpb; CCAAT/enhancer binding protein beta [KO:K10048]
22032  Traf4; TNF receptor associated factor 4 [KO:K09848]
56489  Ikbke; inhibitor of kappaB kinase epsilon [KO:K07211] [EC:2.7.11.10]
30940  Usp25; ubiquitin specific peptidase 25 [KO:K11849] [EC:3.4.19.12]
22033  Traf5; TNF receptor-associated factor 5 [KO:K09849]
22030  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
110809  Srsf1; serine and arginine-rich splicing factor 1 [KO:K12890]
15568  Elavl1; ELAV like RNA binding protein 1 [KO:K13088]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
14825  Cxcl1; C-X-C motif chemokine ligand 1 [KO:K05505]
20310  Cxcl2; C-X-C motif chemokine ligand 2 [KO:K05505]
330122  Cxcl3; C-X-C motif chemokine ligand 3 [KO:K05505]
20311  Cxcl5; C-X-C motif chemokine ligand 5 [KO:K05506]
15945  Cxcl10; C-X-C motif chemokine ligand 10 [KO:K12671]
20296  Ccl2; C-C motif chemokine ligand 2 [KO:K14624]
20293  Ccl12; C-C motif chemokine ligand 12 [KO:K14624]
20306  Ccl7; C-C motif chemokine ligand 7 [KO:K05509]
20297  Ccl20; C-C motif chemokine ligand 20 [KO:K14625]
16193  Il6; interleukin 6 [KO:K05405]
21926  Tnf; tumor necrosis factor [KO:K03156]
19225  Ptgs2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
12985  Csf3; colony stimulating factor 3 (granulocyte) [KO:K05423]
12981  Csf2; colony stimulating factor 2 (granulocyte-macrophage) [KO:K05427]
56519  Defb4; defensin beta 4 [KO:K21100]
116746  Defb6; defensin beta 6 [KO:K21100]
27358  Defb3; defensin beta 3 [KO:K21100]
17833  Muc5ac; mucin 5, subtypes A and C, tracheobronchial/gastric [KO:K13908]
74180  Muc5b; mucin 5, subtype B, tracheobronchial [KO:K13908]
20201  S100a8; S100 calcium binding protein A8 (calgranulin A) [KO:K21127]
20202  S100a9; S100 calcium binding protein A9 (calgranulin B) [KO:K21128]
16819  Lcn2; lipocalin 2 [KO:K21129]
83995  Mmp1a; matrix metallopeptidase 1a (interstitial collagenase) [KO:K01388] [EC:3.4.24.7]
83996  Mmp1b; matrix metallopeptidase 1b (interstitial collagenase) [KO:K01388] [EC:3.4.24.7]
17392  Mmp3; matrix metallopeptidase 3 [KO:K01394] [EC:3.4.24.17]
17395  Mmp9; matrix metallopeptidase 9 [KO:K01403] [EC:3.4.24.35]
17386  Mmp13; matrix metallopeptidase 13 [KO:K07994] [EC:3.4.24.-]
234836  Il17c; interleukin 17C [KO:K05491]
57890  Il17re; interleukin 17 receptor E [KO:K05168]
16176  Il1b; interleukin 1 beta [KO:K04519]
15978  Ifng; interferon gamma [KO:K04687]
56069  Il17b; interleukin 17B [KO:K05490]
239114  Il17d; interleukin 17D [KO:K05492]
Reference
PMID:23917206
  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
PMID:23557798
  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
PMID:24011563
  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
PMID:25145755
  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
PMID:21349428
  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
PMID:20514051
  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
PMID:22324470
  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
PMID:26252407
  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
PMID:21074482
  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
PMID:21852080
  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
PMID:18701318
  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
PMID:21155836
  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
PMID:20383173
  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
PMID:20177959
  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
PMID:19575028
  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
PMID:18178098
  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
PMID:23116200
  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
PMID:17027518
  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
PMID:21130872
  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
PMID:17921324
  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
PMID:22851696
  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
PMID:17177681
  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
mmu04010  MAPK signaling pathway
mmu04060  Cytokine-cytokine receptor interaction
mmu04064  NF-kappa B signaling pathway
mmu04210  Apoptosis
mmu04659  Th17 cell differentiation
KO pathway
ko04657   
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