Interleukin-11 signaling pathway (WP3159)

Bos taurus

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. Please access this pathway at [http://www.netpath.org/netslim/IL_11_pathway NetSlim] database.

Authors

Martina Summer-Kutmon , Alex Pico , and Eric Weitz

Activity

last edited

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Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

interleukin-11 signaling pathway

Participants

Label Type Compact URI Comment
IKBKB GeneProduct ensembl:ENSBTAG00000007599 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3551
IL6ST GeneProduct ensembl:ENSBTAG00000017745 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3572
IL11RA GeneProduct ensembl:ENSBTAG00000014907 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3590
IL11RA GeneProduct ensembl:ENSBTAG00000014907 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3590
IL6ST GeneProduct ensembl:ENSBTAG00000017745 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3572
YES1 GeneProduct ensembl:ENSBTAG00000001523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7525
JAK2 GeneProduct ensembl:ENSBTAG00000012047 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
STAT3 GeneProduct ensembl:ENSBTAG00000021523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
IL11 GeneProduct ensembl:ENSBTAG00000047400 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3589
IL11 GeneProduct ensembl:ENSBTAG00000047400 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3589
PIK3R1 GeneProduct ensembl:ENSBTAG00000010989 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
PPP2R4 GeneProduct ensembl:ENSBTAG00000001933 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5524
RAF1 GeneProduct ensembl:ENSBTAG00000045748 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
HRAS GeneProduct ensembl:ENSBTAG00000046644 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3265
PTPN11 GeneProduct ensembl:ENSBTAG00000002048 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
GRB2 GeneProduct ensembl:ENSBTAG00000004736 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
FYN GeneProduct ensembl:ENSBTAG00000011851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2534
RPS6 GeneProduct ensembl:ENSBTAG00000014449 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6194
RPS6KA1 GeneProduct ensembl:ENSBTAG00000014447 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6195
AKT1 GeneProduct ensembl:ENSBTAG00000017636 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
MAPK3 GeneProduct ensembl:ENSBTAG00000016156 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
MAPK1 GeneProduct ensembl:ENSBTAG00000010312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
STAT1 GeneProduct ensembl:ENSBTAG00000007867 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
CREB1 GeneProduct ensembl:ENSBTAG00000005474 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1385
ATF1 GeneProduct ensembl:ENSBTAG00000018131 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:466
CHUK GeneProduct ensembl:ENSBTAG00000007591 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1147
RELA GeneProduct ensembl:ENSBTAG00000013895 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
BIRC5 GeneProduct ensembl:ENSBTAG00000013573 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:332
BCL2 GeneProduct ensembl:ENSBTAG00000019302 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:596
SOCS3 GeneProduct ensembl:ENSBTAG00000008441 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
RUNX2 GeneProduct ensembl:ENSBTAG00000004104 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:860
BGLAP GeneProduct ensembl:ENSBTAG00000009433 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:632
IBSP GeneProduct ensembl:ENSBTAG00000000470 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3381
ICAM1 GeneProduct ensembl:ENSBTAG00000010303 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3383
SOCS3 GeneProduct ensembl:ENSBTAG00000008441 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
SRC GeneProduct ensembl:ENSBTAG00000008938 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
JAK1 GeneProduct ensembl:ENSBTAG00000003147 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
STAT3 GeneProduct ensembl:ENSBTAG00000021523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
TYK2 GeneProduct ensembl:ENSBTAG00000011698 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7297
MAP2K1 GeneProduct ensembl:ENSBTAG00000033983 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
MAP2K2 GeneProduct ensembl:ENSBTAG00000024450 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
RPS6KB1 GeneProduct ensembl:ENSBTAG00000016851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6198
RELA GeneProduct ensembl:ENSBTAG00000013895 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
FES GeneProduct ensembl:ENSBTAG00000002941 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2242
TGFB1 GeneProduct ensembl:ENSBTAG00000020457 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7040
PIAS1 GeneProduct ensembl:ENSBTAG00000005564 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8554
PIAS3 GeneProduct ensembl:ENSBTAG00000021634 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10401
PIAS1 GeneProduct ensembl:ENSBTAG00000005564 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8554
PIAS3 GeneProduct ensembl:ENSBTAG00000021634 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10401
ITGA2 GeneProduct ensembl:ENSBTAG00000019289 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3673
STAT1 GeneProduct ensembl:ENSBTAG00000007867 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
PDPK1 GeneProduct ensembl:ENSBTAG00000034436 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5170

References