Interleukin 6 signal transducer (gp130, oncostatin M receptor)
| Gp130 crystal structure from PDB 1p9m.
| Available structures: 1bj8, 1bqu, 1i1r, 1p9m, 1pvh
|| IL6ST; CD130; CDw130; GP130; GP130-RAPS; IL6R-beta
| External IDs
|| OMIM: 600694 MGI: 96560 Homologene: 1645
| Molecular Function:
|| • receptor activity|
• interleukin-6 receptor activity
• oncostatin-M receptor activity
• protein binding
| Cellular Component:
|| • plasma membrane|
• integral to plasma membrane
| Biological Process:
|| • immune response|
• cell surface receptor linked signal transduction
• positive regulation of cell proliferation
• regulation of Notch signaling pathway
|| NM_002184 (mRNA)|
|| Chr 13: 113.58 - 113.63 Mb
| Pubmed search
Glycoprotein 130 (also known as gp130, IL6ST or CD130) is a transmembrane protein which is the founding member of the class of tall cytokine receptors. It forms one subunit of type I cytokine receptors within the IL-6 receptor family. It is often referred to as the common gp130 subunit, and is important for signal transduction following cytokine engagement. As with other type I cytokine receptors, gp130 possesses a WSXWS amino acid motif that ensures correct protein folding and ligand binding. It interacts with Janus kinases to elicit an intracellular signal following receptor interaction with its ligand. Structurally, gp130 is composed of five fibronectin type-III domains and one immunoglobulin-like C2-type (immunoglobulin-like) domain in its extracellular portion.
Additional recommended knowledge
The members of the IL-6 receptor family all complex with gp130 for signal transduction. For example, IL-6 binds to the IL-6 Receptor. The complex of these two proteins then associates with gp130. This complex of 3 proteins then homodimerizes to form a hexameric complex which can produce downstream signals. There are many other proteins which associate with gp130, such as cardiotrophin 1 (CT-1), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), and IL-11. There are also several other proteins which have structural similarity to gp130 and contain the WSXWS motif and preserved cysteine residues. Members of this group include LIF-R, OSM-R, and G-CSF-R.
Loss of gp130
gp130 is an important part of many different types of signaling complexes. Inactivation of gp130 is lethal to mice. Homozygous mice who are born show a number of defects including impaired development of the ventricular myocardium. Haematopoietic effects included reduced numbers of stem cells in the spleen and liver.
gp130 has no intrinsic tyrosine kinase activity. Instead, it is phosphorylated on tyrosine residues after complexing with other proteins. The phosphorylation leads to association with JAK/Tyk tyrosine kinases and STAT protein transcription factors. In particular, STAT-3 is activated which leads to the activation of many downstream genes. Other pathways activated include RAS and MAPK signaling.
- ^ Hibi et al. (1990). "Molecular cloning and expression of an IL-6 signal transducer, gp130". Cell 63: 1149-1157.
- ^ Bravo et al (1998). "Crystal structure of a cytokine-binding region of gp130". EMBO J 17: 1665-1674.
- ^ Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T, Kishimoto T (1993). "IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase". Science 260: 1808-1810.
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- ^ Kishimoto T, Taga T, Akira S (1994). "Cytokine signal transduction". Cell 76: 253-262.
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- Schiemann WP, Bartoe JL, Nathanson NM (1997). "Box 3-independent signaling mechanisms are involved in leukemia inhibitory factor receptor alpha- and gp130-mediated stimulation of mitogen-activated protein kinase. Evidence for participation of multiple signaling pathways which converge at Ras.". J. Biol. Chem. 272 (26): 16631-6. PMID 9195977.
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- Kim H, Baumann H (1998). "Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells.". J. Biol. Chem. 272 (49): 30741-7. PMID 9388212.
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- Barton VA, Hudson KR, Heath JK (1999). "Identification of three distinct receptor binding sites of murine interleukin-11.". J. Biol. Chem. 274 (9): 5755-61. PMID 10026196.
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|Transmembrane receptors: immune receptors|
|Cytokine receptor||Type I: interleukin (IL-2, IL-3) - CSF (Erythropoietin, GM-CSF, G-CSF) - Glycoprotein 130/Oncostatin M - Leukemia inhibitory factor - common subunits (Common gamma chain, CSF2RB)|
Type II: interleukin (IL22RA2) - interferon (IFNAR, IFNGR)
Other: Chemokine - TGF-beta - Tumor necrosis factor
|Pattern recognition/Toll-like||TLR 1 - TLR 2 - TLR 3 - TLR 4 - TLR 5 - TLR 6 - TLR 7 - TLR 8 - TLR 9 - TLR 10|
|Fc receptor||ε (FcεRI, FcεRII) - γ (FcγRI, FcγRII, FcγRIII) - α/μ (FcαRI, Fcα/μR) - Neonatal|
|Lymphocyte homing receptor||CD44 - L-selectin - VLA-4 - LFA-1|
|other||Antigen receptor (B-cell, T cell) - Complement - Formyl peptide - Immunophilins - Integrin - Killer-cell immunoglobulin-like - Scavenger|