Interleukin-11 Signaling Pathway (Homo sapiens)

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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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History

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CompareRevisionActionTimeUserComment
71360view18:36, 17 October 2013MaintBotAutomated update of data sources
67406view10:57, 26 June 2013DdiglesOntology Term : 'interleukin-11 signaling pathway' added !
63224view21:03, 8 May 2013MaintBotUpdating gpml version
53108view01:15, 30 October 2012MaintBotModified categories
52830view05:36, 23 October 2012NetPathModified description
52829view05:34, 23 October 2012NetPathNew pathway

External references

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NameTypeDatabase referenceComment
IBSPGeneProduct3381 (Entrez Gene)
ATF1GeneProduct466 (Entrez Gene)
PIK3R2GeneProduct5296 (Entrez Gene)
FESGeneProduct
IL6STGeneProduct3572 (Entrez Gene)
BCL2GeneProduct596 (Entrez Gene)
IL11RAGeneProduct3590 (Entrez Gene)
TYK2GeneProduct7297 (Entrez Gene)
YES1GeneProduct7525 (Entrez Gene)
ITGA2GeneProduct3673 (Entrez Gene)
JAK2GeneProduct3717 (Entrez Gene)
RELAGeneProduct5970 (Entrez Gene)
STAT3GeneProduct6774 (Entrez Gene)
RUNX2GeneProduct860 (Entrez Gene)
IL11GeneProduct3589 (Entrez Gene)
SRCGeneProduct6714 (Entrez Gene)
PIK3R1GeneProduct5295 (Entrez Gene)
MAP2K2GeneProduct
PPP2R4GeneProduct5524 (Entrez Gene)
PIAS1GeneProduct8554 (Entrez Gene)
RAF1GeneProduct5894 (Entrez Gene)
IKBKBGeneProduct3551 (Entrez Gene)
HRASGeneProduct3265 (Entrez Gene)
CHUKGeneProduct1147 (Entrez Gene)
PTPN11GeneProduct5781 (Entrez Gene)
BIRC5GeneProduct332 (Entrez Gene)
GRB2GeneProduct2885 (Entrez Gene)
SOCS3GeneProduct9021 (Entrez Gene)
FYNGeneProduct2534 (Entrez Gene)
BGLAPGeneProduct632 (Entrez Gene)
RPS6GeneProduct6194 (Entrez Gene)
ICAM1GeneProduct3383 (Entrez Gene)
RPS6KA1GeneProduct6195 (Entrez Gene)
JAK1GeneProduct3716 (Entrez Gene)
AKT1GeneProduct207 (Entrez Gene)
MAP2K1GeneProduct
MAPK3GeneProduct5595 (Entrez Gene)
RPS6KB1GeneProduct
MAPK1GeneProduct5594 (Entrez Gene)
TGFB1GeneProduct7040 (Entrez Gene)
STAT1GeneProduct6772 (Entrez Gene)
PIAS3GeneProduct10401 (Entrez Gene)
CREB1GeneProduct1385 (Entrez Gene)
PDPK1GeneProduct5170 (Entrez Gene)
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