GP130 (Glycoprotein 130, also known as IL6ST or IL-6 Signal Transducer) is a common signal-transducing receptor subunit used by multiple interleukin-6 family cytokines[1]. As a key component of the IL-6 family cytokine receptor complex, GP130 is essential for signaling through JAK/STAT, MAPK, and PI3K/Akt pathways. Given its central role in cytokine signaling, GP130 has been implicated in neuroinflammation, neuronal survival, and neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and multiple sclerosis[2].
.infobox.infix-protein
; Protein Name
: Glycoprotein 130 (GP130)
; Gene Symbol
: IL6ST
; UniProt ID
: P40189
; Molecular Weight
: ~130 kDa (917 amino acids)
; Subcellular Localization
: Cell membrane, cytoplasm (after ligand binding)
; Protein Family
: IL-6 receptor family (gp130 family)
; Tissue Distribution
: Ubiquitous, high expression in liver, immune cells, brain
GP130 (encoded by IL6ST gene) is a 917-amino acid transmembrane protein that serves as the common signal-transducing receptor subunit for the interleukin-6 (IL-6) family of cytokines[3]. This family includes IL-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), and IL-27.
The extracellular region contains:
Immunoglobulin-like Domain (1-100 aa):
Cytokine-binding homology region (CHR):
Fibronectin type III domains:
Contains critical signaling motifs:
Box1 motif: JAK binding site
Box2 motif: Additional JAK interaction
Multiple tyrosine residues: STAT docking sites
GP130 activates JAK tyrosine kinases[4]:
JAK Activation:
STAT Phosphorylation:
Gene Transcription:
GP130 also activates MAPK signaling:
GP130 is central to neuroinflammatory responses[5]:
Astrocyte Activation:
Microglial Activation:
In neurons, GP130 signaling:
GP130 is important for oligodendrocytes:
GP130 has complex roles in AD[6]:
Neuroinflammation:
Neuroprotective Effects:
Therapeutic Targeting:
In PD, GP130 signaling may[7]:
GP130 is relevant to MS:
In ALS:
GP130 is a drug target:
Inhibitors:
Agonists:
GP130 levels may indicate:
Genetic variants may affect:
The study of Gp130 Protein Il 6 Signal Transducer 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.
Kishimoto T, et al. (1995). IL-6 family of cytokines and GP130. Blood. PMID:7540141 ↩︎
Scheller J, et al. (2011). The IL-6 family of cytokines. Cold Spring Harb Perspect Biol. PMID:21934100 ↩︎
Heinrich PC, et al. (2003). Principles of interleukin-6-type cytokine signalling. Biochem J. PMID:12689679 ↩︎
O'Shea JJ, et al. (2015). JAK/STAT pathways. N Engl J Med. PMID:26606758 ↩︎
Erta M, et al. (2012). IL-6 in the nervous system. Int J Biol Sci. PMID:22298955 ↩︎
Ringheim GE, et al. (1995). Interleukin-6 and Alzheimer's disease. Neuroscience. PMID:8786794 ↩︎
Bolin LM, et al. (2002). Neurotrophic effects of IL-6. Exp Neurol. PMID:11958850 ↩︎