IL6 signaling pathway (WP364)

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 the 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. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP364 CPTAC Assay Portal]
last edited

Authors

A.Pandey, MaintBot, Khanspers, MartijnVanIersel, NetPath, Christine Chichester, Mkutmon, Joppe014, Zari, Susan, L Dupuis, Egonw, and Eweitz

Cited In

Organism

Homo sapiens

Communities

CPTAC

Annotations

Pathway Ontology: interleukin-6 signaling pathway Interleukin mediated signaling pathway

Participants

Label Type Compact Identifier
MAP2K1 Protein ncbigene:5604
IL6 Protein ncbigene:3569
STAT3 Protein ncbigene:6774
GRB2 Protein ncbigene:2885
MAPK3 Protein ncbigene:5595
STAT1 Protein ncbigene:6772
SOS1 Protein ncbigene:6654
MAP2K2 Protein ncbigene:5605
MAP2K4 Protein ncbigene:6416
PRKCD Protein ncbigene:5580
GAB1 Protein ncbigene:2549
MAPK1 Protein ncbigene:5594
RPS6KB1 Protein ncbigene:6198
HCK Protein ncbigene:3055
AKT1 Protein ncbigene:207
PIK3R1 Protein ncbigene:5295
RAC1 Protein ncbigene:5879
GSK3B Protein ncbigene:2932
SHC1 Protein ncbigene:6464
IL6R Protein ncbigene:3570
STAT3 Protein ncbigene:6774
VAV1 Protein ncbigene:7409
IL6ST Protein ncbigene:3572
JAK1 Protein ncbigene:3716
PIK3R2 Protein ncbigene:5296
JAK2 Protein ncbigene:3717
SOCS3 Protein ncbigene:9021
STAT1 Protein ncbigene:6772
BAD Protein ncbigene:572
TYK2 Protein ncbigene:7297
PTPN11 Protein ncbigene:5781
IL6R Protein ncbigene:3570
IL6 Protein ncbigene:3569
IL6ST Protein ncbigene:3572
PRDM1 Protein ncbigene:639
STAT1 Protein ncbigene:6772
MAP3K7 Protein ncbigene:6885
STAT3 Protein ncbigene:6774
STAT3 Protein ncbigene:6774
IRF1 Protein ncbigene:3659
BCL2L1 Protein ncbigene:598
STAT1 Protein ncbigene:6772
STAT1 Protein ncbigene:6772
CREBBP Protein ncbigene:1387
VIP Protein ncbigene:7432
STAT3 Protein ncbigene:6774
STAT1 Protein ncbigene:6772
A2M Protein mirbase.mature:ENSG00000175899
CRP Protein ncbigene:1401
JUNB Protein ncbigene:3726
STAT3 Protein ncbigene:6774
HDAC1 Protein ncbigene:3065
TIMP1 Protein ncbigene:7076
STAT3 Protein ncbigene:6774
NLK Protein ncbigene:51701
NCOA1 Protein ncbigene:8648
STAT1 Protein ncbigene:6772
EP300 Protein ncbigene:2063
IL6ST Protein ncbigene:3572
STAT1 Protein ncbigene:6772
AGT Protein ncbigene:183
STAT3 Protein ncbigene:6774
MAP3K7 Protein ncbigene:6885

References

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