IL-6 Signaling
Interleukin 6 (IL-6) is considered a regulator of acute-phase responses and a lymphocyte stimulatory factor. The central role of IL-6 in inflammation makes it an important target for the management of infectious and inflammatory diseases. IL-6 responses are transmitted through Glycoprotein 130 (GP130), which serves as the universal signal-transducing receptor subunit for all IL-6-related cytokines.IL-6-type cytokines utilize tyrosine kinases of the Janus Kinase (JAK) family and signal transducers and activators of transcription (STAT) family as major mediators of signal transduction. Upon receptor stimulation by IL-6, the JAK family of kinases associated with GP130 are activated, resulting in the phosphorylation of GP130...
Pathway Summary
Interleukin 6 (IL-6) is considered a regulator of acute-phase responses and a lymphocyte stimulatory factor. The central role of IL-6 in inflammation makes it an important target for the management of infectious and inflammatory diseases. IL-6 responses are transmitted through Glycoprotein 130 (GP130), which serves as the universal signal-transducing receptor subunit for all IL-6-related cytokines.IL-6-type cytokines utilize tyrosine kinases of the Janus Kinase (JAK) family and signal transducers and activators of transcription (STAT) family as major mediators of signal transduction. Upon receptor stimulation by IL-6, the JAK family of kinases associated with GP130 are activated, resulting in the phosphorylation of GP130. Several phosphotyrosine residues of GP130 serve as docking sites for STAT factors mainly STAT3 and STAT1. Subsequently, STATs are phosphorylated, form dimers and translocate to the nucleus, where they regulate transcription of target genes.In addition to the JAK/STAT pathway of signal transduction, IL-6 also activates the extracellular signal-regulated kinases (ERK1/2) of the mitogen activated protein kinase (MAPK) pathway. The upstream activators of ERK1/2 include RAS and the src homology-2 containing proteins GRB2 and SHC. The SHC protein is activated by JAK2 and thus serves as a link between the IL-6 activated JAK/STAT and RAS-MAPK pathways.The phosphorylation of MAPKs in response to IL-6 activated RAS results in the activation of nuclear factor IL-6 (NF-IL6), which in turn stimulates the transcription of the IL-6 gene. The transcription of the IL-6 gene is also stimulated by tumor necrosis factor (TNF) and Interleukin-1 (IL-1) via the activation of nuclear factor kappa B (NFκB).This pathway highlights the important molecular components involved in IL-6 signaling.
IL-6 Signaling Genes list
Explore Genes related to IL-6 Signaling
A2Malpha-2-macroglobulin ABCB1ATP binding cassette subfamily B member 1 AKT1AKT serine/threonine kinase 1 AKT2AKT serine/threonine kinase 2 AKT3AKT serine/threonine kinase 3 CD14CD14 molecule CEBPBCCAAT enhancer binding protein beta CHUKcomponent of inhibitor of nuclear factor kappa B kinase complex COL1A1collagen type I alpha 1 chain CRPC-reactive protein CSNK2A1casein kinase 2 alpha 1 CSNK2A2casein kinase 2 alpha 2 CSNK2A3casein kinase 2 alpha 3 CSNK2Bcasein kinase 2 beta CXCL8C-X-C motif chemokine ligand 8 CYP19A1cytochrome P450 family 19 subfamily A member 1 ELK1ETS transcription factor ELK1 ELP1elongator acetyltransferase complex subunit 1 ERASES cell expressed Ras FOSFos proto-oncogene, AP-1 transcription factor subunit GRB2growth factor receptor bound protein 2 HRASHRas proto-oncogene, GTPase HSPB1heat shock protein family B (small) member 1 HSPB2heat shock protein family B (small) member 2 HSPB3heat shock protein family B (small) member 3 HSPB7heat shock protein family B (small) member 7 IKBKBinhibitor of nuclear factor kappa B kinase subunit beta IKBKEinhibitor of nuclear factor kappa B kinase subunit epsilon IKBKGinhibitor of nuclear factor kappa B kinase regulatory subunit gamma IL18interleukin 18 IL18RAPinterleukin 18 receptor accessory protein IL1Ainterleukin 1 alpha IL1Binterleukin 1 beta IL1F10interleukin 1 family member 10 IL1R1interleukin 1 receptor type 1 IL1R2interleukin 1 receptor type 2 IL1RAPinterleukin 1 receptor accessory protein IL1RAPL1interleukin 1 receptor accessory protein like 1 IL1RAPL2interleukin 1 receptor accessory protein like 2 IL1RL1interleukin 1 receptor like 1 IL1RL2interleukin 1 receptor like 2 IL1RNinterleukin 1 receptor antagonist IL33interleukin 33 IL36Ainterleukin 36 alpha IL36Binterleukin 36 beta IL36Ginterleukin 36 gamma IL36RNinterleukin 36 receptor antagonist IL37interleukin 37 IL6interleukin 6 IL6Rinterleukin 6 receptor IL6STinterleukin 6 signal transducer JAK2Janus kinase 2 JUNJun proto-oncogene, AP-1 transcription factor subunit KRASKRAS proto-oncogene, GTPase LBPlipopolysaccharide binding protein MAP2K1mitogen-activated protein kinase kinase 1 MAP2K2mitogen-activated protein kinase kinase 2 MAP2K3mitogen-activated protein kinase kinase 3 MAP2K4mitogen-activated protein kinase kinase 4 MAP2K6mitogen-activated protein kinase kinase 6 MAP2K7mitogen-activated protein kinase kinase 7 MAP3K14mitogen-activated protein kinase kinase kinase 14 MAP3K7mitogen-activated protein kinase kinase kinase 7 MAP4K4mitogen-activated protein kinase kinase kinase kinase 4 MAPK1mitogen-activated protein kinase 1 MAPK10mitogen-activated protein kinase 10 MAPK11mitogen-activated protein kinase 11 MAPK12mitogen-activated protein kinase 12 MAPK13mitogen-activated protein kinase 13 MAPK14mitogen-activated protein kinase 14 MAPK3mitogen-activated protein kinase 3 MAPK8mitogen-activated protein kinase 8 MAPK9mitogen-activated protein kinase 9 MAPKAPK2MAPK activated protein kinase 2 MCL1MCL1 apoptosis regulator, BCL2 family member MRASmuscle RAS oncogene homolog NFKB1nuclear factor kappa B subunit 1 NFKB2nuclear factor kappa B subunit 2 NFKBIANFKB inhibitor alpha NFKBIBNFKB inhibitor beta NFKBIDNFKB inhibitor delta NFKBIENFKB inhibitor epsilon NGFRnerve growth factor receptor NRASNRAS proto-oncogene, GTPase PIK3C2Aphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PIK3C2Bphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta PIK3C2Gphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma PIK3C3phosphatidylinositol 3-kinase catalytic subunit type 3 PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3R1phosphoinositide-3-kinase regulatory subunit 1 PIK3R2phosphoinositide-3-kinase regulatory subunit 2 PIK3R3phosphoinositide-3-kinase regulatory subunit 3 PIK3R4phosphoinositide-3-kinase regulatory subunit 4 PIK3R5phosphoinositide-3-kinase regulatory subunit 5 PIK3R6phosphoinositide-3-kinase regulatory subunit 6 PTPN11protein tyrosine phosphatase non-receptor type 11 RAF1Raf-1 proto-oncogene, serine/threonine kinase RALARAS like proto-oncogene A RALBRAS like proto-oncogene B RAP1ARAP1A, member of RAS oncogene family RAP1BRAP1B, member of RAS oncogene family RAP2ARAP2A, member of RAS oncogene family RAP2BRAP2B, member of RAS oncogene family RASD1ras related dexamethasone induced 1 RASD2RASD family member 2 RELREL proto-oncogene, NF-kB subunit RELARELA proto-oncogene, NF-kB subunit RELBRELB proto-oncogene, NF-kB subunit RRASRAS related RRAS2RAS related 2 SHC1SHC adaptor protein 1 SOCS1suppressor of cytokine signaling 1 SOCS3suppressor of cytokine signaling 3 SOS1SOS Ras/Rac guanine nucleotide exchange factor 1 SOS2SOS Ras/Rho guanine nucleotide exchange factor 2 SRFserum response factor STAT3signal transducer and activator of transcription 3 TAB1TGF-beta activated kinase 1 (MAP3K7) binding protein 1 TNFtumor necrosis factor TNFAIP6TNF alpha induced protein 6 TNFRSF11BTNF receptor superfamily member 11b TNFRSF1ATNF receptor superfamily member 1A TNFRSF1BTNF receptor superfamily member 1B TRAF2TNF receptor associated factor 2 TRAF6TNF receptor associated factor 6 VEGFAvascular endothelial growth factor A