IL-1 signaling pathway (Bos taurus)

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IL-1 Signaling PathwayCYCYCYNUNUNURELANFKBIBMAP2K1TRAF6TRAF6AKT1MAPK14TRAF6PIK3R2UBE2V1TAB3Ca 2+IL1RAPIL1APRKCZMAP2K2TRAF6TOLLIPMAP2K7PTPN11IKBKGRELRELAIKBKGMAPK1BIKBAUBE2NMAP2K6MAP3K14IL1R1CCL2RELECSITNFKB1NFKB1PELI1MAP3K7IP1MAPK3TRAF6MAP2K4TOLLIPMAP3K3MAPKAPK2IKBKBHSPB2IL1RAPPLCG1CHUKMAP3K1PIK3R1PELI2TAB2MAPK8MYD88IL1R1MAP3K2SQSTM1MAP2K3MAPK9MYD88IL1BPPPPPPPPPPPPPPPPPPPPPUbPPPPPPPPIRAK4IRAK1UbIRAKMIRAK2MAP3K7PMAPK14JUNPATF2PMAPK9PPMAPK8PCYNUNUCYProteinProtein - protein dissociationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageReceptorProteinmRNALigandEnzyme complex


Description

The IL-1 family of cytokines currently consists of 11 members which are encoded by distinct genes and includes IL-1α, IL-1β, and the IL-1 Receptor antagonist (IL-1RA). The major role of IL-1 type cytokines is to control pro-inflammatory reactions in response to tissue injury - either due to pathogen-associated molecular patterns (PAMPs) or Danger associated molecular patterns (DAMPs). Interleukin-1 (IL-1), which includes IL-1α and IL-1β, plays a crucial role in many auto inflammatory diseases. IL- 1α and IL-1β are produced predominantly by macrophages and monocytes, and to a lesser extent by other cell types such as epithelial cells endothelial cells and fibroblasts. IL-1 alpha, is a membrane anchored protein which signals through autocrine or juxtracrine mechanisms where as the soluble IL-1β acts in a paracrine or systemic manner. Significant progress has been achieved in the study of the signaling events mediated by IL-1 and the processes they control. Involvement of IL-1α or IL-1β in host responses to infections caused by intracellular microorganisms such as Mycobacterium tuberculosis as well as in autoinflammatory diseases makes its signaling components important candidates for drug targetting for these diseases. The two forms of IL-1 (IL-1α and IL-1β) bind to the same cellular receptor, the Type I IL- 1 receptor (IL-1RI) to induce signaling. Upon receptor engagement, IL-1R1 forms a heterodimer with IL-1 receptor accessory protein (IL-1RAcP), which functions as a co receptor. IL-1RAcP cannot bind directly to IL-1 but is essential for IL-1-mediated signaling. Binding of IL-1 to this receptor complex leads to the activation of the transcription factor NF-κB through different signaling mechanisms. Two IL-1 receptor-associated kinases, IRAK-1 and IRAK-2 have been implicated in the activation of NF-κB. IRAK 1 and 2 functions as adapter proteins and protein kinases to transmit downstream signals. It recruits TRAF6 to the IL-1 receptor complex via an interaction with IL-1RAcP. Oligomerization of TRAF6 and subsequent formation of TAK1 and MEKK3 signaling complexes relays the signal via NF-κB-inducing kinase (NIK) to two I-kappaB kinases (IKK-1 and -2), leading to NF-kappaB activation. Activation of other mitogen activated protein kinases, including JNKs and p38 MAPK through various MAP2Ks also play important roles in mediating IL-1 responses by activating transcription through the AP-1 transcription factor. The above mentioned signaling events co-operatively induce the expression of IL-1 target genes such as CCL2, IL-8 and IL-6. The interactions and intersections between canonical and non-canonical Interleukin-1 signaling systems are depicted in the pathway map. Regulation of IL-1 signaling can be brought about by various mechanisms. The IL-1 family member IL-1RA can bind to the IL1-R1 receptor with similar affinity as IL-1α and β, but is incapable of activating the signaling response. The type II IL-1 receptor can bind to IL-1 alpha and beta but lacks signaling capacity. The naturally occurring 'shed' domains of the extracellular IL-1 receptor chains (IL-1RI, IL-1RII and IL- 1RAcP) also act as inhibitors of IL-1 signaling. In the cell, IL-1R binds to toll- interacting protein (TOLLIP), which results in the inhibition of IRAK1 and by promoting efficient degradation of IL-1R by targeting the internalized receptor to endosomes. Other mechanisms such as p38MAPK mediated phosphorylation of TAB1 which results in the inactivation of TAK1, and expression of genes including MAPK phosphatase 1 (MKP-1) and Inhibitor of kappa B alpha (NFKBIA) that inhibit IL-1 signaling components also serve as negative regulators of IL-1 signaling.

Please access this pathway at NetSlim database.

If you use this pathway, you must cite following paper:

Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K. C., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S. K., Lin, J., Houtman, J. C. D., Desiderio, S., Renauld, J., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. and Pandey, A. (2010). NetPath: A public resource of curated signal transduction pathways. Genome Biology. 11:R3.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP195(79965) with a 95.0% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

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History

CompareRevisionActionTimeUserComment
89935view13:45, 6 October 2016MkutmonOntology Term : 'interleukin-1 signaling pathway' added !
89934view13:44, 6 October 2016MkutmonModified description
80920view15:31, 30 June 2015MkutmonNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1ProteinENSBTAG00000017636 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
ATF2ProteinENSBTAG00000002295 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1386
BIKBAProteinENSBTAG00000016683 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4792
CCL2RnaENSBTAG00000037811 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6347
CHUKProteinENSBTAG00000007591 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1147
Ca 2+MetaboliteHMDB00464 (HMDB)
ECSITProteinENSBTAG00000015049 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51295
HSPB2ProteinHomologyConvert: Multiple homologues found: En:ENSBTAG00000000440;En:ENSBTAG00000000440;
IKBKBProteinENSBTAG00000007599 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3551
IKBKGProteinENSBTAG00000006268 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8517
IL1AProteinENSBTAG00000010349 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3552
IL1BProteinENSBTAG00000001321 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3553
IL1R1ProteinENSBTAG00000005273 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3554
IL1RAPProteinENSBTAG00000013205 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3556
IRAK1ProteinENSBTAG00000016085 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3654
IRAK2ProteinENSBTAG00000006193 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3656
IRAK4ProteinENSBTAG00000021105 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51135
IRAKMProteinENSBTAG00000007636 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:11213
JUNProteinENSBTAG00000004037 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3725
MAP2K1ProteinENSBTAG00000033983 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
MAP2K2ProteinENSBTAG00000024450 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
MAP2K3ProteinENSBTAG00000010576 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5606
MAP2K4ProteinENSBTAG00000012103 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6416
MAP2K6ProteinENSBTAG00000001609 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5608
MAP2K7ProteinENSBTAG00000010639 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5609
MAP3K14ProteinENSBTAG00000007084 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000006062
MAP3K1ProteinENSBTAG00000013790 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4214
MAP3K2ProteinENSBTAG00000004216 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10746
MAP3K3ProteinENSBTAG00000008151 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4215
MAP3K7ProteinENSBTAG00000002625 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6885
MAP3K7IP1ProteinENSBTAG00000019828 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10454
MAPK14ProteinENSBTAG00000020783 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
MAPK1ProteinENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK3ProteinENSBTAG00000016156 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
MAPK8ProteinENSBTAG00000007876 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
MAPK9ProteinENSBTAG00000004709 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5601
MAPKAPK2ProteinENSBTAG00000038107 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9261
MYD88ProteinENSBTAG00000000563 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4615
NFKB1ProteinENSBTAG00000020270 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790
NFKBIBProteinENSBTAG00000001778 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4793
PELI1ProteinENSBTAG00000020865 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:57162
PELI2ProteinENSBTAG00000005141 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:57161
PIK3R1ProteinENSBTAG00000010989 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
PIK3R2ProteinHomologyConvert: Multiple homologues found: En:ENSBTAG00000002350;En:ENSBTAG00000002350;
PLCG1ProteinENSBTAG00000017584 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5335
PRKCZProteinENSBTAG00000014119 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5590
PTPN11ProteinENSBTAG00000002048 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
RELAProteinENSBTAG00000013895 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
RELProteinENSBTAG00000015386 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5966
SQSTM1ProteinENSBTAG00000015591 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8878
TAB2ProteinENSBTAG00000013454 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23118
TAB3ProteinENSBTAG00000048159 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:257397
TOLLIPProteinENSBTAG00000008237 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:54472
TRAF6ProteinENSBTAG00000036009 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7189
UBE2NProteinENSBTAG00000021767 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7334
UBE2V1ProteinHomologyConvert: Multiple homologues found: En:ENSBTAG00000027316;En:ENSBTAG00000010135;

Annotated Interactions

No annotated interactions
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