IL-11 Signaling Pathways

Click on the other IL-6 family cytokines listed below to see the signaling pathways that are activated by each cytokine. Refer to the table below each pathway to see a select list of cytokine-expressing cells or tissues and the primary biological effects induced by the different members of the IL-6 cytokine family.

sIL-11 R alpha
sIL-11 R alpha
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IL-11
IL-11
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IL-11
IL-11
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gp130
gp130
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sIL-11 R
alpha
sIL-11 R
alpha
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IL-11
IL-11
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gp130
gp130
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IL-11
IL-11
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sIL-11 R
alpha
sIL-11 R
alpha
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gp130
gp130
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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Trans Signaling
Trans Signaling
IL-11 Signaling
IL-11 Signaling
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IL-11
IL-11
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sIL-11 R alpha
sIL-11 R alpha
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IL-11
IL-11
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IL-11 R alpha
IL-11 R alpha
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IL-11
IL-11
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gp130
gp130
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IL-11 R
alpha
IL-11 R
alpha
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IL-11
IL-11
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gp130
gp130
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gp130
gp130
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IL-11
IL-11
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IL-11 R
alpha
IL-11 R
alpha
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gp130
gp130
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IL-11
IL-11
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IL-11 R alpha
IL-11 R alpha
Classic Signaling
Classic Signaling
IL-11 R Complex
IL-11 R Complex
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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Tyk2
Tyk2
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Jak2
Jak2
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Jak1
Jak1
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IRS1/2
IRS1/2
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SHP-2
SHP-2
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Grb2
Grb2
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SOS
SOS
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Gab1/2
Gab1/2
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PI 3-K
PI 3-K
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PIP2
PIP2
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PIP3
PIP3
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PDK-1
PDK-1
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Akt/PKB
Akt/PKB
Cell Survival
Cell Proliferation
Cell Survival
Cell Proliferation
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TSC1/2
(Inactive)
TSC1/2
(Inactive)
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Rheb
Rheb
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GTP
GTP
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mTORC1
mTORC1
p70 S6K
p70 S6K
RPS6
RPS6
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4EBP1
4EBP1
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eIF4E
eIF4E
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eIF4E
eIF4E
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4EBP1
4EBP1
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Protein Synthesis
Protein Synthesis
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STAT1
STAT1
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STAT3
STAT3
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STAT5
STAT5
STAT Dimer
STAT Dimer
STAT Dimer
STAT Dimer
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SHP-2 or SHC
SHP-2 or SHC
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Grb2
Grb2
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SOS
SOS
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Gab1/2
Gab1/2
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Vav
Vav
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Rac1
Rac1
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MAPKKK
(Unknown)
MAPKKK
(Unknown)
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MKK-4
MKK-4
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p38
p38
JNK
JNK
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PKC delta
PKC delta
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AP-1
AP-1
Cell Proliferation
Cell Proliferation
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Ras
Ras
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Raf
Raf
MEK1/2
MEK1/2
ERK1/2
ERK1/2
p90 RSK
p90 RSK
Transcription Factor
Transcription Factor

Overview of IL-11 Signaling Pathways

IL-11 is a member of the IL-6 cytokine family, which also includes IL-6, IL-27 p28/IL-30, IL-31, Leukemia inhibitory factor (LIF), Oncostatin M (OSM), Cardiotrophin-like cytokine (CLC), Ciliary neurotrophic factor (CNTF), Cardiotrophin-1 (CT-1), and Neuropoietin. Like most other members of the IL-6 cytokine family, IL-11 is a four-helix bundle cytokine that signals through a receptor complex containing the gp130 receptor subunit. Similar to both IL-6 and CNTF, IL-11 can promote both classic and trans-signaling pathways. Classic IL-11 signaling is initiated in cells expressing the membrane-bound form of the IL-11 receptor alpha subunit (IL-11 R alpha) and gp130. IL-11 initially binds with low affinity to membrane-bound IL-11 R alpha, which then recruits the signal-transducing gp130 receptor subunit to form a high affinity receptor complex. Association of gp130 with the IL-11-IL-11 R alpha complex stimulates gp130 dimerization and formation of a 2:2:2 heterohexameric complex. Additionally, IL-11 can initiate trans-signaling in gp130-expressing cells that lack expression of IL-11 R alpha. IL-11 trans-signaling requires binding of IL-11 to a soluble form of IL-11 R alpha, which can be generated by proteolytic cleavage. This IL-11/soluble IL-11 R alpha complex can then trans-activate IL-11 signaling pathways in gp130-expressing cells, thereby expanding the range of cells that are affected by IL-11. Formation of either the IL-11 classic or trans-signaling ligand-receptor complexes leads to the activation of several intracellular signaling pathways including the Jak-STAT pathway, the Ras-MAPK pathway, the PI 3-K-Akt pathway, and the p38 and JNK MAPK pathways, which mediate various biological effects in different cell types.

IL-11 was originally discovered in the supernatant of a stromal cell line as a factor that could stimulate the IL-6-dependent proliferation of plasmacytoma cells. It was subsequently shown to be produced by multiple different cell types and to have a wide range of activities. These include the ability to stimulate thrombopoiesis and erythropoiesis, promote the production, differentiation, and maturation of megakaryocytes, and act synergistically with other hematopoietic growth factors. IL-11 has also been shown to have immunomodulatory functions such as the ability to regulate macrophage differentiation and function, induce Th2 and/or Th17 polarization of CD4+ T cells, stimulate B cell IgG production, and protect endothelial cells from inflammation-associated injuries. Additionally, it can regulate neurogenesis, increase osteoclast development, inhibit adipogenesis, and regulate epithelial cell proliferation and apoptosis.

To learn more, please visit our IL-6 Family Research Area page.

IL-11

Primary IL-11-Expressing Cells Primary Biological Effects of IL-11
Bone marrow stromal cells Promotes the production, differentiation, and maturation of megakaryocytes
Chondrocytes Stimulates thrombopoiesis and erythropoiesis
Epithelial cells Modulates the growth of gastrointestinal epithelial cells; Confers mucosal protection in the intestine
Eosinophils Increases osteoclast development and bone resorption
Fibroblasts Regulates neurogenesis; May act as a differentiation factor for neural progenitors
Hepatocytes Inhibits adipogenesis
Intestinal myofibroblasts Regulates macrophage differentiation and function
Keratinocytes Induces Th2 or Th17 polarization of CD4+ T cells
Macrophages Promotes B cell IgG production
Neurons Generally considered to be an anti-inflammatory cytokine
Osteoblasts Protects endothelial cells from immune-mediated injuries
Smooth muscle cells Stimulates production of several acute phase proteins in hepatocytes
Synoviocytes Regulates epithelial cell proliferation and apoptosis
T cells  
Trophoblasts  

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