Interleukin-11 signaling pathway (WP2332)

Homo sapiens

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 [ NetSlim] database. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


NetPath , Daniela Digles , Zahra Roudbari , Kristina Hanspers , Eric Weitz , Lauren J. Dupuis , and Egon Willighagen


last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.


Homo sapiens



Pathway Ontology

interleukin-11 signaling pathway


Label Type Compact Identifier Comment
IKBKB GeneProduct ncbigene:3551
PIK3R2 GeneProduct ncbigene:5296
IL6ST GeneProduct ncbigene:3572
IL11RA GeneProduct ncbigene:3590
IL11RA GeneProduct ncbigene:3590
IL6ST GeneProduct ncbigene:3572
YES1 GeneProduct ncbigene:7525
JAK2 GeneProduct ncbigene:3717
STAT3 GeneProduct ncbigene:6774
IL11 GeneProduct ncbigene:3589
IL11 GeneProduct ncbigene:3589
PIK3R1 GeneProduct ncbigene:5295
PPP2R4 GeneProduct ncbigene:5524
RAF1 GeneProduct ncbigene:5894
HRAS GeneProduct ncbigene:3265
PTPN11 GeneProduct ncbigene:5781
GRB2 GeneProduct ncbigene:2885
FYN GeneProduct ncbigene:2534
RPS6 GeneProduct ncbigene:6194
RPS6KA1 GeneProduct ncbigene:6195
AKT1 GeneProduct ncbigene:207
MAPK3 GeneProduct ncbigene:5595
MAPK1 GeneProduct ncbigene:5594
STAT1 GeneProduct ncbigene:6772
CREB1 GeneProduct ncbigene:1385
ATF1 GeneProduct ncbigene:466
CHUK GeneProduct ncbigene:1147
RELA GeneProduct ncbigene:5970
BIRC5 GeneProduct ncbigene:332
BCL2 GeneProduct ncbigene:596
SOCS3 GeneProduct ncbigene:9021
RUNX2 GeneProduct ncbigene:860
BGLAP GeneProduct ncbigene:632
IBSP GeneProduct ncbigene:3381
ICAM1 GeneProduct ncbigene:3383
SOCS3 GeneProduct ncbigene:9021
SRC GeneProduct ncbigene:6714
JAK1 GeneProduct ncbigene:3716
STAT3 GeneProduct ncbigene:6774
TYK2 GeneProduct ncbigene:7297
MAP2K1 GeneProduct ncbigene:5604
MAP2K2 GeneProduct ncbigene:5605
RPS6KB1 GeneProduct ncbigene:6198
RELA GeneProduct ncbigene:5970
FES GeneProduct ncbigene:2242
TGFB1 GeneProduct ncbigene:7040
PIAS1 GeneProduct ncbigene:8554
PIAS3 GeneProduct ncbigene:10401
PIAS1 GeneProduct ncbigene:8554
PIAS3 GeneProduct ncbigene:10401
ITGA2 GeneProduct ncbigene:3673
STAT1 GeneProduct ncbigene:6772
PDPK1 GeneProduct ncbigene:5170