IL-6 signaling pathway (WP976)

Bos taurus

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 [http://www.netpath.org/netslim/IL_6_pathway.html NetSlim] database. If you use this pathway, please 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.

Authors

Martina Summer-Kutmon and Egon Willighagen

Activity

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Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

interleukin-6 signaling pathway Interleukin mediated signaling pathway

Participants

Label Type Compact URI Comment
MAP2K1 Protein ensembl:ENSBTAG00000033983 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
IL6 Protein ensembl:ENSBTAG00000014921 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3569
STAT3 Protein ensembl:ENSBTAG00000021523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
GRB2 Protein ensembl:ENSBTAG00000004736 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
MAPK3 Protein ensembl:ENSBTAG00000016156 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
STAT1 Protein ensembl:ENSBTAG00000007867 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
SOS1 Protein ensembl:ENSBTAG00000011643 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6654
MAP2K2 Protein ensembl:ENSBTAG00000024450 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
MAP2K4 Protein ensembl:ENSBTAG00000012103 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6416
PRKCD Protein ensembl:ENSBTAG00000008719 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5580
GAB1 Protein ensembl:ENSBTAG00000002813 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
MAPK1 Protein ensembl:ENSBTAG00000010312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
RPS6KB1 Protein ensembl:ENSBTAG00000016851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6198
HCK Protein ensembl:ENSBTAG00000007932 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3055
AKT1 Protein ensembl:ENSBTAG00000017636 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
PIK3R1 Protein ensembl:ENSBTAG00000010989 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
RAC1 Protein ensembl:ENSBTAG00000009233 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
GSK3B Protein ensembl:ENSBTAG00000048057 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2932
SHC1 Protein ensembl:ENSBTAG00000019838 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
IL6R Protein ensembl:ENSBTAG00000018474 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3570
VAV1 Protein ensembl:ENSBTAG00000039160 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7409
IL6ST Protein ensembl:ENSBTAG00000017745 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3572
JAK1 Protein ensembl:ENSBTAG00000003147 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
JAK2 Protein ensembl:ENSBTAG00000012047 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
SOCS3 Protein ensembl:ENSBTAG00000008441 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
BAD Protein ensembl:ENSBTAG00000012511 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:572
TYK2 Protein ensembl:ENSBTAG00000011698 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7297
PTPN11 Protein ensembl:ENSBTAG00000002048 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
PRDM1 Protein ensembl:ENSBTAG00000000816 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:639
MAP3K7 Protein ensembl:ENSBTAG00000002625 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6885
IRF1 Protein ensembl:ENSBTAG00000031231 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3659
BCL2L1 Protein ensembl:ENSBTAG00000006526 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:598
CREBBP Protein ensembl:ENSBTAG00000026403 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1387
VIP Protein ensembl:ENSBTAG00000013400 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7432
A2M Protein ensembl:ENSBTAG00000018137 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2
CRP Protein ensembl:ENSBTAG00000013907 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1401
JUNB Protein ensembl:ENSBTAG00000012046 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3726
HDAC1 Protein ensembl:ENSBTAG00000012698 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3065
TIMP1 Protein ensembl:ENSBTAG00000005043 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7076
NLK Protein ensembl:ENSBTAG00000014825 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51701
NCOA1 Protein ensembl:ENSBTAG00000015007 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8648
NR2F6 Protein ensembl:ENSBTAG00000011136 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2063
AGT Protein ensembl:ENSBTAG00000012393 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:183

References

  1. NetPath: a public resource of curated signal transduction pathways. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GSS, Venugopal AK, et al. Genome Biol. 2010 Jan 12;11(1):R3. PubMed Europe PMC Scholia