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Oncostatin M Signaling Pathways

Click on the other IL-6 family cytokines shown in the Explore Pathways box 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.

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OSM
Oncostatin M (OSM)
Oncostatin M (OSM)
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OSM
Type I
Type I
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Type II
Type II
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LIF R
LIF R
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OSM
OSM
OSM
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OSM
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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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OSM R beta
OSM R beta
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OSM
OSM
OSM
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OSM
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gp130
gp130
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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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MEK5
MEK5
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ERK5
ERK5
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PI 3-K
PI 3-K
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PKC delta
PKC delta
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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
Ras
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Ras
Raf
Raf
MEK1/2
MEK1/2
ERK1/2
ERK1/2
p90 RSK
p90 RSK
Transcription Factor
Transcription Factor
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Oncostatin M Signaling Pathways

Overview of Oncostatin M (OSM) Signaling Pathways

Oncostatin M (OSM) is a member of the IL-6 cytokine family, which also includes IL-6, IL-11, IL-27 p28/IL-30, IL-31, Leukemia inhibitory factor (LIF), Cardiotrophin-like cytokine (CLC), Ciliary neurotrophic factor (CNTF), Cardiotrophin-1 (CT-1), and Neuropoietin. OSM is produced primarily by activated monocytes and macrophages, activated T cells, dendritic cells, neutrophils, and osteoblasts. Like other IL-6 family cytokines, OSM is a long chain four alpha-helix bundle cytokine with up-up-down-down topology, but it is unique in that it can signal through two different receptor complexes. The type I OSM receptor complex consists of LIF R and gp130, while the type II OSM receptor complex consists of OSM R and gp130. OSM initially binds with low affinity to gp130 and then recruits either LIF R or OSM R. LIF R, OSM R, and gp130 all associate with members of the Jak family of tyrosine kinases through their cytoplasmic domains, leading to the phosphorylation, dimerization, and nuclear translocation of STAT family proteins, predominantly STAT3, STAT5, and STAT1. In addition, OSM signaling triggers activation of the Ras-MAPK pathway, the PI 3-K-Akt pathway, the p38 and JNK MAPK pathways, and PKC delta.

OSM was originally discovered as a cytokine capable of inhibiting the growth of melanoma cells and has subsequently been found to have a wide range of effects on different cell types. It has been shown to regulate the formation and maintenance of the bone marrow niche required for hematopoiesis, to suppress adipocyte differentiation and promote osteoblast differentiation of mesenchymal stem cells, and to regulate inflammatory responses. OSM is capable of both promoting and inhibiting inflammation depending on the target cell and the other cytokines present in the microenvironment. In the liver, OSM was found to regulate the acute phase response, as well as hepatocyte proliferation and tissue remodeling during liver regeneration. Additionally, OSM has been shown to regulate the development of the central nervous system, induce the dedifferentiation of cardiomyocytes, regulate the production of other cytokines and growth factors by endothelial cells, and stimulate angiogenesis.

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

Primary OSM-Expressing Cells Primary Biological Effects of OSM
Activated monocytes/macrophages Regulates the formation and maintenance of the hematopoietic microenvironment
Activated T cells Regulates mesenchymal stem cell differentiation; Suppresses adipocyte differentiation
Dendritic cells Regulates hepatocyte proliferation and tissue remodeling during liver regeneration; Regulates the acute phase response
Neutrophils Induces cardiomyocyte dedifferentiation
Osteoblasts Regulates bone formation and resorption
  Neuroregulatory
  Regulates the development of nociceptive neurons in the dorsal root ganglia
  Regulates inflammatory responses
  Regulates the production of other cytokines and growth factors by endothelial cells; Stimulates angiogenesis

Oncostatin M Signaling Pathways background image 1