Il6St Interleukin 6 Signal Transducer (Gp130) plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
| IL6ST / gp130 | |
|---|---|
| Gene Symbol | IL6ST |
| Full Name | Interleukin 6 Signal Transducer |
| Alias | gp130, CD130 |
| NCBI Gene ID | 3572 |
| UniProt ID | P40189 |
| Chromosomal Location | 5q11.2 |
| Protein Class | Type I Cytokine Receptor |
| Molecular Weight | ~130 kDa |
| Expression | Ubiquitous (neurons, astrocytes, microglia, oligodendrocytes) |
IL6ST (Interleukin 6 Signal Transducer), commonly known as gp130, is the founding member and signal-transducing subunit of the interleukin-6 (IL-6) family of cytokines. This ubiquitous signaling receptor is essential for mediating the effects of at least nine different cytokines, making it a central hub for cytokine signaling in the immune system and central nervous system. gp130 plays critical roles in neural development, synaptic plasticity, neuroinflammation, and neuron survival, with implications for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS)[1].
The IL6ST gene is located on chromosome 5q11.2 and spans approximately 28 kb. The gene consists of 18 exons that encode the 917-amino acid protein. Multiple alternatively spliced isoforms have been identified, including a soluble form that can act as a natural antagonist[2].
gp130 contains multiple functional domains:
Extracellular Domain (~600 aa)
Transmembrane Domain (~22 aa)
Intracellular Domain (~277 aa)
gp130 serves as the common signal-transducing subunit for multiple cytokines:
| Cytokine | Primary Receptor | Biological Function |
|---|---|---|
| IL-6 | IL6Rα | Acute phase response, B cell differentiation |
| IL-11 | IL11Rα | Platelet production, bone remodeling |
| LIF | LIFR | Motor neuron survival, neural stem cell maintenance |
| CNTF | CNTFRα | Motor neuron survival, astrocyte differentiation |
| OSM | OSMR | Stromal cell activation, inflammation |
| CT-1 | LIFR | Cardiac development, neuroprotection |
| NP (Cardiotrophin-1-like) | LIFR | Neuroprotection |
| IL-27 | IL27RA/WSX-1 | T cell differentiation, inflammation |
| IL-35 | IL12RB1/IL27RA | Immunosuppression |
All IL-6 family cytokines signal through a two-receptor system:
The JAK/STAT pathway is the principal signaling cascade:
gp130 also activates pro-survival signaling:
Differentiation and growth signals:
gp130 signaling is essential for nervous system development:
In the mature nervous system, gp130 continues to play important roles:
gp130 signaling has complex and context-dependent effects in AD:
gp130 plays roles in PD pathogenesis:
gp130 signaling is particularly relevant to ALS:
gp130 signaling has dual roles in MS:
This severe disorder involves gp130 pathway dysfunction:
Following ischemic injury, gp130 signaling is activated:
| Agent | Target Cytokine | Status | Indication |
|---|---|---|---|
| Recombinant IL-6 | IL-6R/gp130 | Research | Neuroprotection |
| Recombinant LIF | LIFR/gp130 | Preclinical | ALS, stroke |
| Recombinant CNTF | CNTFRα/gp130 | Research | Motor neuron disease |
| Hyper-IL-6 | IL-6R/gp130 | Preclinical | Neuroinflammation |
| Agent | Mechanism | Status | Indication |
|---|---|---|---|
| Tocilizumab | IL-6R antibody | Approved | Rheumatoid arthritis |
| Sarilumab | IL-6R antibody | Approved | Rheumatoid arthritis |
| Soluble gp130 | Decoy receptor | Research | Chronic inflammation |
[1] Taga T, Hibi M, Hirata Y, et al. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. EMBO J. 1989;8(10):2859-2865.
[2] Heinrich PC, Behrmann I, Haan S, et al. Principles of IL-6-type cytokine signalling. Biochem J. 2003;374(Pt 1):1-20.
[3] Nicola NA, Babon JJ. Leukemia inhibitory factor (LIF). Growth Factors. 2015;33(6):407-418.
[4] Bauer S, Kerr BJ, Patterson PH. The neuropoietic cytokine family in development, plasticity, and disease. Brain Res Rev. 2007;55(1):4-13.
[5] Gadient RA, Otten U. Interleukin-6 (IL-6): a molecule with both beneficial and destructive potentials. Prog Neurobiol. 1997;52(5):379-390.
[6] Murphy PG, Borthwick LS, Altmon M, et al. CNTF receptor alpha is expressed by astrocytes in the adult mouse brain. Glia. 1999;27(1):43-50.
[7] Kerr BJ, Patterson PH. Cytokines as mediators of CNS disease. Mol Neurobiol. 2004;29(2):155-166.
[8] Deverman BE, Patterson PH. Cytokines and CNS development. Neuron. 2009;64(1):61-78.
Il6St Interleukin 6 Signal Transducer (Gp130) plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
The study of Il6St Interleukin 6 Signal Transducer (Gp130) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[1] Taga T, Hibi M, Hirata Y, et al. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. EMBO Journal. 1989;8(10):2859-2865.
[2] Heinrich PC, Behrmann I, Haan S, et al. Principles of IL-6-type cytokine signalling. Biochemical Journal. 2003;374(Pt 1):1-20.
[3] Nicola NA, Babon JJ. Leukemia inhibitory factor (LIF). Growth Factors. 2015;33(6):407-418.
[4] Bauer S, Kerr BJ, Patterson PH. The neuropoietic cytokine family in development, plasticity, and disease. Brain Research Reviews. 2007;55(1):4-13.
[5] Gadient RA, Otten U. Interleukin-6 (IL-6): a molecule with both beneficial and destructive potentials. Progress in Neurobiology. 1997;52(5):379-390.
[6] Murphy PG, Borthwick LS, Altmon M, et al. CNTF receptor alpha is expressed by astrocytes in the adult mouse brain. Glia. 1999;27(1):43-50.
[7] Kerr BJ, Patterson PH. Cytokines as mediators of CNS disease. Molecular Neurobiology. 2004;29(2):155-166.
[8] Deverman BE, Patterson PH. Cytokines and CNS development. Neuron. 2009;64(1):61-78.