Interleukin-11 Signaling Pathway (Bos taurus)

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IKBKBPPIK3R2PIL6STIL11RAOsteoblastic differentiation of periodontal ligament cells Migration of chondrosarcoma cellsEndometrial epithelial cell adhesionInterleukin-11 Signaling PathwayInhibitionGastric inflammation and associated tumorigenesisPhosphatidicTh2 polarization ofIL11RAIL6STPYES1PJAK2STAT3PPIL11IL11PIK3R1PPPP2R4RAF1HRASPPTPN11GRB2PFYNRPS6PRPS6KA1PPAKT1PMAPK3MAPK1PPSTAT1PCREB1ATF1PPCHUKPRELAPBIRC5BCL2SOCS3RUNX2BGLAPIBSPICAM1Phospholipase DSOCS3SRCPJAK1PSTAT3PTYK2PMAP2K1MAP2K2RPS6KB1PRELAFESPacidCD4+ T cellsTGFB1Regulation of macrophage effector functionPIAS1PIAS3PIAS1PIAS3ITGA2 Antiapoptotic effects to support mucosal integrityCYNUCYNUCYNUSTAT1PCYNUPDPK1PProteinTransportPositive regulation of gene expressionLeads to through unknown mechanismTranslocation Induced catalysisProtein-protein interactionLEGENDNucleusCytoplasmCYNUmRNAReceptorLigandProteinLeads to positive regulation of gene expressionSmall moleculeProteinInduced activation


Description

IL-11 is a multifunctional cytokine that belongs to the gp130 family. It was first isolated from a primate bone marrow derived cell line, PU-34 for its ability to stimulate the proliferation of a plasmacytoma cell line, T1165 which was dependent on IL-6. This cytokine plays an important role in the synthesis, maturation and differentiation of hematopoietic cells. It also plays significant role in the inhibition of adipocyte differentiation, regulation of trophoblasts invasion and placentation in humans.

The receptor for IL-11 is IL11RA that uses the common gp130 receptor subunit for signal transduction. The pathways that are activated upon IL-11 stimulation are JAK-STAT, Ras-MAPK, PI3K-AKT and NF-kappa B/p65. Binding of IL-11 with IL-11RA results in the heterodimerization, tyrosine phosphorylation and activation of gp130. The activated IL11RA-gp130 receptor complex further activates Jak family of tyrosine kinases, JAK1 and JAK2. Phosphorylated JAK2 then activates STAT3 and STAT1 that results in their subsequent translocation into the nucleus. The translocated STAT3 then induces the transcription of genes associated with endometrial cell adhesion, gastric inflammation and differentiation of periodontal ligament cells. The activation of STAT3 was shown to be inhibited by the overexpression of Suppressor of cytokine signalling 3 (SOCS3). IL-11 signalling through JAK2/STAT3 has been shown to be crucial for normal placentation in humans and normal development of craniofacial bones and teeth in mice.

In addition to JAK-STAT, IL-11 also activate the Ras-MAPK, PI3K-AKT and NF-kappa B pathways. In response to IL-11, GTP loaded Ras interacts with RAF1 and leads to autophosphorylation of RAF1. Activation of RAF1 leads to the tyrosine phosphorylation and activation of mitogen activated protein kinases (MAPKs) through MEK1 and MEK2. Activation of phospholipase D was triggered by IL-11 leading to the formation of phosphatidic acid, which has also been shown to activate the MAPKs. Transcription factors, ATF1 and CREB1 were activated by these phosphorylated MAPKs through p90 S6 kinase. PI3K-AKT and NF-kappa B/p65 pathways stimulated by IL-11 have been shown to enhance the migration and proliferation of chondrosarcoma cells. In CD4+ T cells, Th2 polarization was induced by IL-11 through NF-kappa B inhibition. SRC, FYN and YES, members of Src family of tyrosine kinases were also activated in response to IL-11 signalling.

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Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP2332(79525) with a 98.0% conversion rate.

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History

CompareRevisionActionTimeUserComment
91170view21:07, 15 January 2017AlexanderPicoFixed unconnected interactions
80726view15:23, 30 June 2015MkutmonNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1GeneProductENSBTAG00000017636 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
ATF1GeneProductENSBTAG00000018131 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:466
BCL2GeneProductENSBTAG00000019302 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:596
BGLAPGeneProductENSBTAG00000009433 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:632
BIRC5GeneProductENSBTAG00000013573 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:332
CHUKGeneProductENSBTAG00000007591 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1147
CREB1GeneProductENSBTAG00000005474 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1385
FESGeneProductENSBTAG00000002941 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2242
FYNGeneProductENSBTAG00000011851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2534
GRB2GeneProductENSBTAG00000004736 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
HRASGeneProductENSBTAG00000046644 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3265
IBSPGeneProductENSBTAG00000000470 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3381
ICAM1GeneProductENSBTAG00000010303 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3383
IKBKBGeneProductENSBTAG00000007599 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3551
IL11GeneProductENSBTAG00000047400 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3589
IL11RAGeneProductENSBTAG00000014907 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3590
IL6STGeneProductENSBTAG00000017745 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3572
ITGA2GeneProductENSBTAG00000019289 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3673
JAK1GeneProductENSBTAG00000003147 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
JAK2GeneProductENSBTAG00000012047 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
MAP2K1GeneProductENSBTAG00000033983 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
MAP2K2GeneProductENSBTAG00000024450 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
MAPK1GeneProductENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK3GeneProductENSBTAG00000016156 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
PDPK1GeneProductENSBTAG00000034436 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5170
PIAS1GeneProductENSBTAG00000005564 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8554
PIAS3GeneProductENSBTAG00000021634 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10401
PIK3R1GeneProductENSBTAG00000010989 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
PIK3R2GeneProductHomologyConvert: Multiple homologues found: En:ENSBTAG00000002350;En:ENSBTAG00000002350;
PPP2R4GeneProductENSBTAG00000001933 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5524
PTPN11GeneProductENSBTAG00000002048 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
RAF1GeneProductENSBTAG00000045748 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
RELAGeneProductENSBTAG00000013895 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
RPS6GeneProductENSBTAG00000014449 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6194
RPS6KA1GeneProductENSBTAG00000014447 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6195
RPS6KB1GeneProductENSBTAG00000016851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6198
RUNX2GeneProductENSBTAG00000004104 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:860
SOCS3GeneProductENSBTAG00000008441 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
SRCGeneProductENSBTAG00000008938 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
STAT1GeneProductENSBTAG00000007867 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
STAT3GeneProductENSBTAG00000021523 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
TGFB1GeneProductENSBTAG00000020457 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7040
TYK2GeneProductENSBTAG00000011698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7297
YES1GeneProductENSBTAG00000001523 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7525

Annotated Interactions

No annotated interactions
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