IL-6 signaling pathway (Bos taurus)

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IL-6 Signaling PathwayMAP2K1PIL6STAT3GRB2MAPK3PSTAT1SOS1PMAP2K2PMAP2K4PPRKCDGAB1PPMAPK1PRPS6KB1HCKPAKT1PIK3R1PRAC1GTPGSK3BSHC1IL6RSTAT3PVAV1PIL6STJAK1PIK3R2JAK2SOCS3STAT1BADPTYK2PTPN11IL6RIL6IL6STSTAT regulated geneexpressionPRDM1STAT1MAP3K7STAT3STAT3IRF1BCL2L1STAT1STAT1CREBBPVIPSTAT3STAT1A2MCRPJUNBSTAT3HDAC1TIMP1STAT3NLKNCOA1STAT1NR2F6IL6STSTAT1AGTSTAT3NUCYNUCYNUCYMAP3K7ProteinProteinmRNALigandReceptorProteinProtein - protein dissociationEnzyme ComplexSmall moleculeInduced activationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageMolecule


Description

IL-6 is a pleiotropic cytokine with important role in immune regulation, hematopoiesis, inflammation and oncogenesis. IL-6-type cytokines exert their action via the signal transducer gp130 that associates with IL6R in a cooperative manner to form a hexameric signal transducing complex, capable of activating the down stream mediators of this signaling pathway. This mechanism of signal transduction is shared by other members of the IL-6 type cytokines like IL-11, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and cardiotrophin-1 that use gp130 as a common subunit of the signal transducing complex. IL-6 stimulation leads to the activation of JAK/STAT pathway. Both STAT1 and STAT3 are phosphorylated and are able to form homo- and heterodimers after activation leading to their nuclear localization and subsequent regulation of transcription of respective target genes. SHP-2 is one of the ubiquitous tyrosine phosphatases and IL-6 stimulation leads to the SHP2-dependent activation of MAPKs, it also links the Grb2-SOS complex and Gab1 to gp130. Phosphorylated Gab1 acts as an adapter and is involved in the indirect association of SHP-2 and PI-3 kinase. Downstream activation of Vav1, Rac-1 and MAP2K4 is necessary for the IL-6-mediated STAT3 phosphorylation and transactivation to accomplish its effects. STAT3 is also phosphorylated by PKCD and it causes inhibition of STAT3 DNA binding and transcriptional activity. PTPN11 and SOCS3 exert inhibitory function and thus lead to down regulation of the signaling cascade.

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 WP364(79962) with a 98.0% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

No bibliography


History

View all...
CompareRevisionActionTimeUserComment
89835view12:09, 6 October 2016MkutmonOntology Term : 'Interleukin mediated signaling pathway' added !
89834view12:09, 6 October 2016MkutmonOntology Term : 'interleukin-6 signaling pathway' added !
89833view12:08, 6 October 2016MkutmonModified description
80777view15:25, 30 June 2015Mkutmonhomology conversion
63400view00:07, 10 May 2013MaintBotUpdated to 2013 gpml schema
40574view19:32, 1 March 2011MaintBotRemoved redundant pathway information and comments
33812view00:21, 9 December 2009MaintBotAutomatic update of empty xrefs
31635view22:23, 13 August 2009MaintBotFixed text labels
30545view21:57, 29 July 2009MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
A2MProteinENSBTAG00000018137 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2
AGTProteinENSBTAG00000012393 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:183
AKT1ProteinENSBTAG00000017636 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
BADProteinENSBTAG00000012511 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:572
BCL2L1ProteinENSBTAG00000006526 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:598
CREBBPProteinENSBTAG00000026403 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1387
CRPProteinENSBTAG00000013907 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1401
GAB1ProteinENSBTAG00000002813 (Ensembl)
  • IL-6 stimulates the tyrosine phosphorylation of Gab1. Gab1 further forms a complex with SHP-2 and the p85 subunit of PI3 kinase in HepG2 cells.
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2549
GRB2ProteinENSBTAG00000004736 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
GSK3BProteinENSBTAG00000048057 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2932
HCKProteinENSBTAG00000007932 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3055
HDAC1ProteinENSBTAG00000012698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3065
IL6ProteinENSBTAG00000014921 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3569
IL6RProteinENSBTAG00000018474 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3570
IL6STProteinENSBTAG00000017745 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3572
IRF1ProteinENSBTAG00000031231 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3659
JAK1ProteinENSBTAG00000003147 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
JAK2ProteinENSBTAG00000012047 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
JUNBProteinENSBTAG00000012046 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3726
MAP2K1ProteinENSBTAG00000033983 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
MAP2K2ProteinENSBTAG00000024450 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
MAP2K4ProteinENSBTAG00000012103 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6416
MAP3K7ProteinENSBTAG00000002625 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6885
MAPK1ProteinENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK3ProteinENSBTAG00000016156 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
NCOA1ProteinENSBTAG00000015007 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8648
NLKProteinENSBTAG00000014825 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51701
NR2F6ProteinENSBTAG00000011136 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2063
PIK3R1ProteinENSBTAG00000010989 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
PIK3R2ProteinHomologyConvert: Multiple homologues found: En:ENSBTAG00000002350;En:ENSBTAG00000002350;
PRDM1ProteinENSBTAG00000000816 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:639
PRKCDProteinENSBTAG00000008719 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5580
PTPN11ProteinENSBTAG00000002048 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
RAC1ProteinENSBTAG00000009233 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
RPS6KB1ProteinENSBTAG00000016851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6198
SHC1ProteinENSBTAG00000019838 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
SOCS3ProteinENSBTAG00000008441 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
SOS1ProteinENSBTAG00000011643 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6654
STAT1ProteinENSBTAG00000007867 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
STAT3ProteinENSBTAG00000021523 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
TIMP1ProteinENSBTAG00000005043 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7076
TYK2ProteinENSBTAG00000011698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7297
VAV1ProteinENSBTAG00000039160 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7409
VIPProteinENSBTAG00000013400 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7432

Annotated Interactions

No annotated interactions
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