Neuropoietin 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.

Neuropoietin (NP)
Neuropoietin (NP)
sCNTF R alpha
sCNTF R alpha
NP
NP
Trans Signaling
Trans Signaling
ProductsClose
LIF R
LIF R
ProductsClose
ProductsClose
gp130
gp130
ProductsClose
ProductsClose
Sortilin
Sortilin
ProductsClose
sCNTF R
alpha
sCNTF R
alpha
NP
NP
ProductsClose
LIF R
LIF R
ProductsClose
ProductsClose
gp130
gp130
ProductsClose
ProductsClose
Tyk2
Tyk2
ProductsClose
ProductsClose
Jak2
Jak2
ProductsClose
ProductsClose
Jak1
Jak1
ProductsClose
ProductsClose
Tyk2
Tyk2
ProductsClose
ProductsClose
Jak2
Jak2
ProductsClose
ProductsClose
Jak1
Jak1
ProductsClose
Neuropoietin Signaling
Neuropoietin Signaling
Classic Signaling
Classic Signaling
CNTF R alpha
CNTF R alpha
NP
NP
ProductsClose
LIF R
LIF R
ProductsClose
ProductsClose
gp130
gp130
ProductsClose
ProductsClose
Sortilin
Sortilin
ProductsClose
CNTF R
alpha
CNTF R
alpha
NP
NP
ProductsClose
LIF R
LIF R
ProductsClose
ProductsClose
gp130
gp130
ProductsClose
ProductsClose
Tyk2
Tyk2
ProductsClose
ProductsClose
Jak2
Jak2
ProductsClose
ProductsClose
Jak1
Jak1
ProductsClose
ProductsClose
Tyk2
Tyk2
ProductsClose
ProductsClose
Jak2
Jak2
ProductsClose
ProductsClose
Jak1
Jak1
ProductsClose
ProductsClose
IRS1/2
IRS1/2
ProductsClose
ProductsClose
SHP-2
SHP-2
ProductsClose
ProductsClose
Grb2
Grb2
ProductsClose
ProductsClose
SOS
SOS
ProductsClose
ProductsClose
Gab1/2
Gab1/2
ProductsClose
PI 3-K
PI 3-K
ProductsClose
We currently do not offer products for this molecule

Use our Product Suggestion form to enter a request.

You will be notified once it becomes available.
PIP2
PIP2
ProductsClose
We currently do not offer products for this molecule

Use our Product Suggestion form to enter a request.

You will be notified once it becomes available.
ProductsClose
PIP3
PIP3
ProductsClose
ProductsClose
PDK-1
PDK-1
ProductsClose
Akt/PKB
Akt/PKB
Cell Survival
Cell Proliferation
Cell Survival
Cell Proliferation
ProductsClose
TSC1/2
(Inactive)
TSC1/2
(Inactive)
ProductsClose
ProductsClose
Rheb
Rheb
ProductsClose
ProductsClose
We currently do not offer products for this molecule

Use our Product Suggestion form to enter a request.

You will be notified once it becomes available.
GTP
GTP
ProductsClose
We currently do not offer products for this molecule

Use our Product Suggestion form to enter a request.

You will be notified once it becomes available.
mTORC1
mTORC1
p70 S6K
p70 S6K
RPS6
RPS6
ProductsClose
4EBP1
4EBP1
ProductsClose
ProductsClose
eIF4E
eIF4E
ProductsClose
ProductsClose
eIF4E
eIF4E
ProductsClose
ProductsClose
4EBP1
4EBP1
ProductsClose
Protein Synthesis
Protein Synthesis
ProductsClose
STAT1
STAT1
ProductsClose
ProductsClose
STAT3
STAT3
ProductsClose
STAT5
STAT5
STAT Dimer
STAT Dimer
STAT Dimer
STAT Dimer
ProductsClose
SHP-2 or SHC
SHP-2 or SHC
ProductsClose
ProductsClose
Grb2
Grb2
ProductsClose
ProductsClose
SOS
SOS
ProductsClose
ProductsClose
Gab1/2
Gab1/2
ProductsClose
ProductsClose
Ras
Ras
ProductsClose
Raf
Raf
MEK1/2
MEK1/2
ERK1/2
ERK1/2
p90 RSK
p90 RSK
Transcription Factor
Transcription Factor

Overview of Neuropoietin (NP) Signaling Pathways

Neuropoietin (NP), also known as Cardiotrophin-2, 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), Oncostatin M (OSM), Cardiotrophin-like cytokine (CLC), Ciliary neurotrophic factor (CNTF), and Cardiotrophin-1 (CT-1). In mice, NP is a long chain four-helix bundle cytokine that is considered to be the product of a gene duplication event involving CT-1. In humans, NP is not expressed due to an 8-nucleotide deletion, suggesting that it exists only as a pseudogene. Mouse NP, similar to CNTF, initially binds to the glycophosphatidylinositol-linked, non-signaling CNTF R alpha receptor subunit, which then recruits the signal-transducing receptor subunits, LIF R and gp130, to form a tripartite receptor complex. Assembly of the LIF R:gp130 heterodimer is enhanced by Sortilin, a member of the Vps10p domain family of type I transmembrane receptors, which binds to CNTF, CLC/CLF-1, and Neuropoietin with high affinity. NP is also thought to be capable of initiating trans-signaling by binding to soluble CNTF R alpha, which is released from the cell surface by phosphatidylinositol-specific phospholipase C. Both the classic and trans-signaling pathways lead to CNTF R:LIF R:gp130 complex formation, and presumably the activation of multiple downstream signaling pathways. Based on the formation of this same tripartite receptor complex by other related IL-6 family cytokines, NP is thought to trigger activation of the Jak-STAT pathway, the Ras-MAPK pathway, and the PI 3-K-Akt pathway. While research on NP has been slow due to the lack of a functional human orthologue, NP has been shown to be specifically expressed during mouse embryonic development. Similar to CLC, CNTF, and CT-1, NP has been shown to promote embryonic motor neuron survival, neural precursor cell proliferation, and astrocyte differentiation in vitro. Significantly, however, NP is expressed when the expression of these other IL-6 family cytokines is low, suggesting that NP may have a unique role in mouse nervous system development.

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

Primary NP-Expressing Tissues Primary Biological Effects of NP
Embryonic neuroepithelium (mouse) Mediates embryonic motor neuron survival
Embryonic cranial and dorsal root sensory ganglia (mouse) Promotes neural precursor cell proliferation
Embryonic spinal cord (mouse) Promotes astrocyte differentiation
Embryonic vibrissae and dermis (mouse) Suggested to have a key role in mouse nervous system development
Embryonic skeletal muscle (mouse) Inhibits adipocyte differentiation and limits glucose uptake by mature adipocytes
  Neuropoietin is not expressed in humans suggesting that it exists only as a pseudogene

Neuropoietin Signaling Pathways background image 1