Interleukin-17 signaling (Homo sapiens)

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3412, 5-7cytosolIL17C IL17RA:IL17RE:IL17CdimerIL17RA IL25 IL17RA IL17A IL25 dimerIL17RB IL17RB IL17A IL17RA IL17RA:IL17RBIL17F IL17RA IL17RA IL17RA IL17C IL25 IL25 IL17RE IL17RE IL17RA:IL17RCligandsIL17RA:IL17RC:IL17RA:IL17RC ligandsIL17RC IL25 IL17RC IL17RA:IL17RCIL17F IL17RA:IL17REIL17C dimerIL17RA:IL17RB:IL25dimer


Description

Interleukin-17 (IL17) is a family of cytokines (Kawaguchi et al. 2004, Gu et al. 2013). IL17A, the founding member of the family, member of this family, is able to induce the production of other cytokines and chemokines, such as IL6, IL8, and granulocyte colony-stimulating factor (G-CSF) in a variety of cell types, including activated T-cells. It plays a pivotal role in host defenses in response to microbial infection, and is involved in the pathogenesis of autoimmune diseases and allergic syndromes. IL17 activates several downstream signalling pathways including NFkB, MAPKs and C/EBPs, inducing the expression of antibacterial peptides, proinflammatory chemokines and cytokines and matrix metalloproteases (MMPs). IL17 can stabilize the mRNA of genes induced by TNF-alpha. IL17 signal transduction is mediated by the cytosolic adaptor molecule Act1 (also known as CIKS).

The receptor for IL17D is unknown (Gu et al. 2013). View original pathway at:Reactome.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114987view16:51, 25 January 2021ReactomeTeamReactome version 75
113431view11:50, 2 November 2020ReactomeTeamReactome version 74
112633view16:01, 9 October 2020ReactomeTeamReactome version 73
101548view11:41, 1 November 2018ReactomeTeamreactome version 66
101083view21:24, 31 October 2018ReactomeTeamreactome version 65
100612view19:58, 31 October 2018ReactomeTeamreactome version 64
100163view16:43, 31 October 2018ReactomeTeamreactome version 63
99713view15:11, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93903view13:43, 16 August 2017ReactomeTeamreactome version 61
93476view11:24, 9 August 2017ReactomeTeamreactome version 61
86955view13:15, 15 July 2016MkutmonOntology Term : 'interleukin-17 family mediated signaling pathway' added !
86573view09:21, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
IL17A ProteinQ16552 (Uniprot-TrEMBL)
IL17C ProteinQ9P0M4 (Uniprot-TrEMBL)
IL17C dimerComplexR-HSA-448410 (Reactome)
IL17F ProteinQ96PD4 (Uniprot-TrEMBL)
IL17RA ProteinQ96F46 (Uniprot-TrEMBL)
IL17RA:IL17RB:IL25 dimerComplexR-HSA-448378 (Reactome)
IL17RA:IL17RBComplexR-HSA-448401 (Reactome)
IL17RA:IL17RC ligandsComplexR-HSA-447091 (Reactome) IL-17A and IL-17F are the best characterized members of the IL-17 cytokine family. Both are covalent homodimers, and also form IL-17A:IL-17F heterodimers.
IL17RA:IL17RC:IL17RA:IL17RC ligandsComplexR-HSA-448403 (Reactome)
IL17RA:IL17RCComplexR-HSA-447089 (Reactome)
IL17RA:IL17RE:IL17C dimerComplexR-HSA-6787823 (Reactome)
IL17RA:IL17REComplexR-HSA-6787821 (Reactome)
IL17RB ProteinQ9NRM6 (Uniprot-TrEMBL)
IL17RC ProteinQ8NAC3 (Uniprot-TrEMBL)
IL17RE ProteinQ8NFR9 (Uniprot-TrEMBL)
IL25 ProteinQ9H293 (Uniprot-TrEMBL)
IL25 dimerComplexR-HSA-448361 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
IL17C dimerR-HSA-5678544 (Reactome)
IL17RA:IL17RB:IL25 dimerArrowR-HSA-447219 (Reactome)
IL17RA:IL17RBR-HSA-447219 (Reactome)
IL17RA:IL17RC ligandsR-HSA-447246 (Reactome)
IL17RA:IL17RC:IL17RA:IL17RC ligandsArrowR-HSA-447246 (Reactome)
IL17RA:IL17RCR-HSA-447246 (Reactome)
IL17RA:IL17RE:IL17C dimerArrowR-HSA-5678544 (Reactome)
IL17RA:IL17RER-HSA-5678544 (Reactome)
IL25 dimerR-HSA-447219 (Reactome)
R-HSA-447219 (Reactome) IL25 (IL17E) binds a receptor complex of IL17RB and IL17RA. Il17rb/Il17ra -/- mice fail to respond to IL25 (Rickel et al. 2008).
R-HSA-447246 (Reactome) Interleukin-17 Receptor A (IL17RA) was identified as the receptor for mammalian interleukin-17A (IL17A) (Yao et al. 1995) though IL17RA bound IL17A with a relatively low affinity, suggesting that there might be additional receptors for IL17A. IL17RA also binds IL17F and is required for IL17F signaling (Hymowitz et al. 2001). IL17RA combines with IL17RC to induce responses to IL17A and IL17F (Toy et al. 2006, Kuestner et al. 2007); the exact stochiometry is not certain but native gel analysis suggests a trimeric complex of two IL17RA subunits and one IL17RC subunit (You et al. 2006). IL17RA could be considered analogous to shared cytokine receptor subunits, such as gp130, which is a common signal transducer for molecules of the IL6 family (Gaffen 2009).
R-HSA-5678544 (Reactome) Interleukin-17 receptor E (IL17RE) is specific for interleukin-17C (IL17C). It has an essential role in host mucosal defense against infection.
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