IL-6 signaling pathway (Rattus norvegicus)

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Plasma membraneSumoylationDMolecular associationECDDCY->NUGODeacetylationENDDMitochondrionRecruitmentAccession Number: NetPath 18DesumoylationAutophosphorylationDephosphorylationCY->NUProteins in a complex interactionNUUbiquitinationEREnzyme complexGene SymbolCY->ENEndosomeCY->NUComplex formationCYNucleusMolecule in the pathwayMethylationDDCY->NULigandGlycosylationCytoplasmTranslocationDControlCY->NUEarly EndosomesMTDInhibitionEndoplasmic reticulumProteolytic cleavageReactions through unknown mechanisms/moleculesPhosphorylationDPalmitoylationReceptorDPMExtracellularGolgi apparatusActivation(Protein-Protein interaction)DDAcetylationDeubiquitinationCY->NUDDemethylationPpp2caStat3Ppp2r2cRGD1561602Ppp2r5eFosSos1Mapk14Map2k2PPP2R5CStat3Il6Ppp2cbJunPpp2r3aAkt1TecPtk2bStat5aCebpbPik3r2Ppp2r2aRGD1565643Inppl1FgrPrkcdJak2LynHrasMap2k6Foxo3aVav1RGD1561201Stat1Ppp2r5dPxnCasp9Raf1Stat3Ppp2r2bCdk5r1Map3k7Jak1PPP2R3BMap3k4Map2k1Stat1DaxxHckArFynIl6stRps6kb1Tnfrsf5Socs3Ppp2r1bStat1Gab2Ptpn11Foxo1aNfkb1Ppp2r4Il6raPlcg1Erbb3SgkCrebbpEif4eTyk2Ptk2Erbb2Ncoa1Stat3Casp3BadMapk14Stat3Nfkb1Rb1Ppp2r5bCdk9Mapk3Rps6ka2Eif2aIl6raGsk3bSgkMaptIl6stMapk1Shc1Grb2Il6RGD1564385Pik3r1Ppp2r1aHspcaMap3k7Hspb1Stat1Hdac1Gab1Cdk5Stat3Ppp2r5aMapkapk2Mapk8Inpp5dCebpbStat3Stat5bBtkStat3Rac1Tcf1Map2k4Eif4ebp1Ep300


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.

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History

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CompareRevisionActionTimeUserComment
125589view19:30, 2 March 2023AlexanderPicoadded description
116986view10:46, 16 May 2021EweitzModified title
83583view07:23, 26 November 2015EgonwAdded two missing gene identifiers.
83528view19:53, 20 November 2015Khanspersupdated missing ids
82974view23:24, 16 November 2015MkutmonUpdated identifiers
82865view16:04, 10 November 2015JmeliusCorrect outdated id
69356view18:53, 8 July 2013MaintBotUpdated to 2013 gpml schema
67383view10:45, 26 June 2013Christine ChichesterOntology Term : 'interleukin-6 signaling pathway' added !
41668view02:35, 2 March 2011MaintBotRemoved redundant pathway information and comments
28140view23:55, 27 January 2009KhanspersChanged name
20965view11:30, 14 November 2008MaintBot[[Pathway:Rattus norvegicus:IL-6 NetPath 18]] moved to [[Pathway:WP135]]: Moved to stable identifier
8192view13:46, 7 January 2008MaintBot[[Pathway:Rat:IL-6 NetPath 18]] moved to [[Pathway:Rattus norvegicus:IL-6 NetPath 18]]: Renaming species
7716view16:12, 18 December 2007MaintBotfixed category names
7255view12:41, 4 November 2007MaintBotAdded categories to GPML
6563view22:20, 22 May 2007A.Pandeygpml file for [[Rat:IL-6_NetPath_18]]

External references

DataNodes

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NameTypeDatabase referenceComment
Akt1GeneProduct24185 (Entrez Gene)
ArGeneProduct24208 (Entrez Gene)
BadGeneProduct64639 (Entrez Gene)
BtkGeneProduct367901 (Entrez Gene)
Casp3GeneProduct25402 (Entrez Gene)
Casp9GeneProduct58918 (Entrez Gene)
Cdk5GeneProduct140908 (Entrez Gene)
Cdk5r1GeneProduct116671 (Entrez Gene)
Cdk9GeneProduct362110 (Entrez Gene)
CebpbGeneProduct24253 (Entrez Gene)
CrebbpGeneProduct54244 (Entrez Gene)
DaxxGeneProduct140926 (Entrez Gene)
Eif2aGeneProduct502531 (Entrez Gene)
Eif4eGeneProduct117045 (Entrez Gene)
Eif4ebp1GeneProduct116636 (Entrez Gene)
Ep300GeneProduct170915 (Entrez Gene)
Erbb2GeneProduct24337 (Entrez Gene)
Erbb3GeneProduct29496 (Entrez Gene)
FgrGeneProduct79113 (Entrez Gene)
FosGeneProduct314322 (Entrez Gene)
Foxo1aGeneProduct84482 (Entrez Gene)
Foxo3aGeneProduct294515 (Entrez Gene)
FynGeneProduct25150 (Entrez Gene)
Gab1GeneProduct361388 (Entrez Gene)
Gab2GeneProduct84477 (Entrez Gene)
Grb2GeneProduct81504 (Entrez Gene)
Gsk3bGeneProduct84027 (Entrez Gene)
HckGeneProduct25734 (Entrez Gene)
Hdac1GeneProduct297893 (Entrez Gene)
HrasGeneProduct293621 (Entrez Gene)
Hspb1GeneProduct24471 (Entrez Gene)
HspcaGeneProduct299331 (Entrez Gene)
Il6GeneProduct24498 (Entrez Gene)
Il6raGeneProductENSRNOG00000020811 (Ensembl)
Il6stGeneProduct25205 (Entrez Gene)
Inpp5dGeneProduct54259 (Entrez Gene)
Inppl1GeneProduct65038 (Entrez Gene)
Jak1GeneProduct84598 (Entrez Gene)
Jak2GeneProduct24514 (Entrez Gene)
JunGeneProduct24516 (Entrez Gene)
LynGeneProduct81515 (Entrez Gene)
Map2k1GeneProduct170851 (Entrez Gene)
Map2k2GeneProduct58960 (Entrez Gene)
Map2k4GeneProduct287398 (Entrez Gene)
Map2k6GeneProduct114495 (Entrez Gene)
Map3k4GeneProduct308106 (Entrez Gene)
Map3k7GeneProduct313121 (Entrez Gene)
Mapk1GeneProduct116590 (Entrez Gene)
Mapk14GeneProduct81649 (Entrez Gene)
Mapk3GeneProduct50689 (Entrez Gene)
Mapk8GeneProduct116554 (Entrez Gene)
Mapkapk2GeneProduct289014 (Entrez Gene)
MaptGeneProductENSRNOG00000005133 (Ensembl)
Ncoa1GeneProduct313929 (Entrez Gene)
Nfkb1GeneProduct81736 (Entrez Gene)
PPP2R3BGeneProduct682033 (Entrez Gene)
PPP2R5CGeneProduct691318 (Entrez Gene)
Pik3r1GeneProduct25513 (Entrez Gene)
Pik3r2GeneProduct29741 (Entrez Gene)
Plcg1GeneProduct25738 (Entrez Gene)
Ppp2caGeneProduct24672 (Entrez Gene)
Ppp2cbGeneProduct24673 (Entrez Gene)
Ppp2r1aGeneProduct117281 (Entrez Gene)
Ppp2r1bGeneProduct315648 (Entrez Gene)
Ppp2r2aGeneProduct117104 (Entrez Gene)
Ppp2r2bGeneProduct60660 (Entrez Gene)
Ppp2r2cGeneProductENSRNOG00000058202 (Ensembl)
Ppp2r3aGeneProduct363122 (Entrez Gene)
Ppp2r4GeneProduct362102 (Entrez Gene)
Ppp2r5aGeneProduct312754 (Entrez Gene)
Ppp2r5bGeneProduct309179 (Entrez Gene)
Ppp2r5dGeneProductENSRNOG00000016849 (Ensembl)
Ppp2r5eGeneProduct299147 (Entrez Gene)
PrkcdGeneProduct170538 (Entrez Gene)
Ptk2GeneProduct25614 (Entrez Gene)
Ptk2bGeneProduct50646 (Entrez Gene)
Ptpn11GeneProduct25622 (Entrez Gene)
PxnGeneProduct360820 (Entrez Gene)
RGD1561201GeneProduct302415 (Entrez Gene)
RGD1561602GeneProduct497961 (Entrez Gene)
RGD1564385GeneProduct361597 (Entrez Gene)
RGD1565643GeneProduct367786 (Entrez Gene)
Rac1GeneProduct363875 (Entrez Gene)
Raf1GeneProduct24703 (Entrez Gene)
Rb1GeneProduct24708 (Entrez Gene)
Rps6ka2GeneProduct117269 (Entrez Gene)
Rps6kb1GeneProduct83840 (Entrez Gene)
SgkGeneProduct29517 (Entrez Gene)
Shc1GeneProduct85385 (Entrez Gene)
Socs3GeneProduct89829 (Entrez Gene)
Sos1GeneProduct313845 (Entrez Gene)
Stat1GeneProduct25124 (Entrez Gene)
Stat3GeneProduct25125 (Entrez Gene)
Stat5aGeneProduct24918 (Entrez Gene)
Stat5bGeneProduct25126 (Entrez Gene)
Tcf1GeneProduct24817 (Entrez Gene)
TecGeneProduct84492 (Entrez Gene)
Tnfrsf5GeneProduct171369 (Entrez Gene)
Tyk2GeneProductENSRNOG00000032948 (Ensembl)
Vav1GeneProduct25156 (Entrez Gene)

Annotated Interactions

No annotated interactions

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