IL6 Signal Transducer (gp130/IL6ST) <table class="infobox infobox-protein">
...
IL6 Signal Transducer (gp130/IL6ST) <table class="infobox infobox-protein">
Overview IL6 Signal Transducer (gp130) is encoded by the IL6ST gene on chromosome 5q11.2. It is the common signal transducing receptor subunit for the interleukin-6 (IL-6) family of cytokines, including IL-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neurotrophic factor (CNTF). gp130 is a critical mediator of neuroinflammation and neurotrophic signaling in the central nervous system.
Structure
Protein Architecture
Length: 917 amino acidsMolecular Weight: ~130 kDa (glycosylated)Domains: Extracellular domain (1-597): Six fibronectin type-III repeats
Transmembrane domain (598-620): Single-pass membrane helix
Cytoplasmic domain (621-917): Janus kinase (JAK) binding and STAT3 docking
Key Functional Motifs
Normal Function
Cytokine Signaling
Coreceptor for IL-6 family cytokines
Activates JAK1/TYK2 kinases upon ligand binding
Dual signaling via STAT3 and MAPK/ERK pathways
Regulates acute phase response and immune cell differentiation
Neuronal Functions
CNTF signaling: Essential for motor neuron survivalLIF signaling: Supports neural stem cell maintenanceIL-6 signaling: Mediates neuroinflammation responsesRegulates synaptic plasticity and memory formation
Role in Neurodegeneration
Alzheimer's Disease
Neuroinflammation IL-6/gp130 promotes microglial activation
Chronic signaling contributes to chronic neuroinflammation
STAT3 activation in reactive [astrocytes](/entities/astrocytes)
[Amyloid-beta](/proteins/amyloid-beta) Interactions IL-6 signaling increases [BACE1](/entities/bace1) expression
Aβ stimulates IL-6 production in astrocytes
Creates feed-forward inflammatory loop
Neuronal Survival CNTF/gp130 signaling provides neuroprotection
Age-related gp130 signaling decline
Therapeutic potential of enhancing gp130 signaling
Parkinson's Disease
Elevated IL-6 in PD patients and CSF
gp130 in dopaminergic neuron survival
Involvement in microglial activation in substantia nigra
Amyotrophic Lateral SALS
CNTF/gp130 pathway dysfunction in motor [neurons](/entities/neurons)
Therapeutic trials of CNTF in ALS (failed due to side effects)
Altered gp130 signaling in astrocytes
Therapeutic Targeting
Agonists
Antagonists
Key Publications [@rosejohn2013]: [Scheller et al., IL-6 family of cytokines](https://pubmed.ncbi.nlm.nih.gov/21393192/). Cold Spring Harbor Perspectives in Biology . 2011;3(12):a012351.
[@heinrich1998]: [Rose-John, IL-6 trans-signaling](https://pubmed.ncbi.nlm.nih.gov/29549634/). Cold Spring Harbor Perspectives in Biology . 2018;10(3):a028449.
[@scheller2011]: [Gadient & Otten, IL-6 in CNS](https://pubmed.ncbi.nlm.nih.gov/9207704/). Progress in Neurobiology . 1997;52(5):379-390.
See Also
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
External Links
[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)
References
[Rose-John S, IL-6 family cytokines and neuroinflammation (2013)](https://pubmed.ncbi.nlm.nih.gov/23588647/)
[Heinrich PC, et al, Interleukin-6-type cytokine signaling through the GP130/JAK/STAT pathway (1998)](https://pubmed.ncbi.nlm.nih.gov/9729272/)
[Scheller J, et al, The IL-6 family of cytokines (2011)](https://pubmed.ncbi.nlm.nih.gov/21872666/)
[O'Shea JJ, et al, JAK/STAT pathway in cytokine signaling in immunity and disease (2010)](https://pubmed.ncbi.nlm.nih.gov/20963088/)
[Ip WK, et al, IL-6 and neuroinflammation in Alzheimer's disease (2017)](https://pubmed.ncbi.nlm.nih.gov/28781886/)
[Hsu MP, et al, IL-6 in neurodegeneration and neurological disorders (2016)](https://pubmed.ncbi.nlm.nih.gov/27160653/)
[Boulanger MJ, et al, Molecular mechanisms of IL-6 family cytokine signaling (2006)](https://pubmed.ncbi.nlm.nih.gov/16934840/)
[Gadient RA, et al, IL-6 in the central nervous system: from physiology to pathology (2000)](https://pubmed.ncbi.nlm.nih.gov/10795653/)
[Spooren A, et al, IL-6 in the hippocampus: role in neuroinflammation and behavior (2010)](https://pubmed.ncbi.nlm.nih.gov/20680824/)
[Campbell IL, et al, Neuroinflammation in transgenic mice expressing IL-6 (1994)](https://pubmed.ncbi.nlm.nih.gov/8166690/) Show full description