Glycoprotein 130

Glycoprotein 130 (also known as gp130, IL6ST, IL6-beta 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. [cite journal | author= Hibi et al. | title=Molecular cloning and expression of an IL-6 signal transducer, gp130 | journal= Cell | year= 1990 | volume= 63 | pages= 1149–1157 | doi=10.1016/0092-8674(90)90411-7] [cite journal | author= Bravo et al | title=Crystal structure of a cytokine-binding region of gp130 | journal= EMBO J | year= 1998 | volume= 17 | pages= 1665–1674 | doi=10.1093/emboj/17.6.1665]

Characteristics

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. [cite journal | author=Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T, Kishimoto T | title=IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase | journal= Science | year= 1993 | volume= 260 | pages= 1808–1810 | doi=10.1126/science.8511589] 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. [cite journal | author= Kishimoto T, Akira S, Narazaki M, Taga T | title=Interleukin-6 family of cytokines and gp130 | journal= Blood | year= 1995 | volume= 86 | pages= 1243–1254] 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. [cite journal | author= Yoshida K, Taga T, Saito M, Suematsu S, Kumanogoh A, Tanaka T, Fujiwara H, Hirata M, Yamagami T, Nakahata T, Hirabayashi T, Yoneda Y, Tanaka K, Wang W-Z, Mori C, Shiota K, Yoshida N, Kishimoto T | title=Targeted disruption of gp130, a common signal transducer for IL-6-family of cytokines, leads to myocardial and hematological disorders | journal= Proc Natl Acad Sci | year= 1996 | volume= 93 | pages= 407–411 | doi=10.1073/pnas.93.1.407] 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.

ignal Transduction

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. [cite journal | author= Kishimoto T, Taga T, Akira S | title=Cytokine signal transduction | journal= Cell | year= 1994 | volume= 76 | pages= 253–262 | doi=10.1016/0092-8674(94)90333-6] In particular, STAT-3 is activated which leads to the activation of many downstream genes. Other pathways activated include RAS and MAPK signaling.

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Ip NY, Nye SH, Boulton TG, "et al." |title=CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130. |journal=Cell |volume=69 |issue= 7 |pages= 1121–32 |year= 1992 |pmid= 1617725 |doi=
*cite journal | author=Hibi M, Murakami M, Saito M, "et al." |title=Molecular cloning and expression of an IL-6 signal transducer, gp130. |journal=Cell |volume=63 |issue= 6 |pages= 1149–57 |year= 1991 |pmid= 2261637 |doi=
*cite journal | author=Taga T, Hibi M, Hirata Y, "et al." |title=Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. |journal=Cell |volume=58 |issue= 3 |pages= 573–81 |year= 1989 |pmid= 2788034 |doi=
*cite journal | author=Rodriguez C, Grosgeorge J, Nguyen VC, "et al." |title=Human gp130 transducer chain gene (IL6ST) is localized to chromosome band 5q11 and possesses a pseudogene on chromosome band 17p11. |journal=Cytogenet. Cell Genet. |volume=70 |issue= 1-2 |pages= 64–7 |year= 1995 |pmid= 7736792 |doi=
*cite journal | author=Narazaki M, Yasukawa K, Saito T, "et al." |title=Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130. |journal=Blood |volume=82 |issue= 4 |pages= 1120–6 |year= 1993 |pmid= 8353278 |doi=
*cite journal | author=Davis S, Aldrich TH, Stahl N, "et al." |title=LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. |journal=Science |volume=260 |issue= 5115 |pages= 1805–8 |year= 1993 |pmid= 8390097 |doi=
*cite journal | author=Murakami M, Hibi M, Nakagawa N, "et al." |title=IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. |journal=Science |volume=260 |issue= 5115 |pages= 1808–10 |year= 1993 |pmid= 8511589 |doi=
*cite journal | author=Sharkey AM, Dellow K, Blayney M, "et al." |title=Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos. |journal=Biol. Reprod. |volume=53 |issue= 4 |pages= 974–81 |year= 1996 |pmid= 8547494 |doi=
*cite journal | author=Mosley B, De Imus C, Friend D, "et al." |title=Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation. |journal=J. Biol. Chem. |volume=271 |issue= 51 |pages= 32635–43 |year= 1997 |pmid= 8999038 |doi=
*cite journal | author=Lee IS, Liu Y, Narazaki M, "et al." |title=Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6. |journal=FEBS Lett. |volume=401 |issue= 2-3 |pages= 133–7 |year= 1997 |pmid= 9013873 |doi=
*cite journal | author=Auguste P, Guillet C, Fourcin M, "et al." |title=Signaling of type II oncostatin M receptor. |journal=J. Biol. Chem. |volume=272 |issue= 25 |pages= 15760–4 |year= 1997 |pmid= 9188471 |doi=
*cite journal | author=Schiemann WP, Bartoe JL, Nathanson NM |title=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. |journal=J. Biol. Chem. |volume=272 |issue= 26 |pages= 16631–6 |year= 1997 |pmid= 9195977 |doi=
*cite journal | author=Diamant M, Rieneck K, Mechti N, "et al." |title=Cloning and expression of an alternatively spliced mRNA encoding a soluble form of the human interleukin-6 signal transducer gp130. |journal=FEBS Lett. |volume=412 |issue= 2 |pages= 379–84 |year= 1997 |pmid= 9256256 |doi=
*cite journal | author=Koshelnick Y, Ehart M, Hufnagl P, "et al." |title=Urokinase receptor is associated with the components of the JAK1/STAT1 signaling pathway and leads to activation of this pathway upon receptor clustering in the human kidney epithelial tumor cell line TCL-598. |journal=J. Biol. Chem. |volume=272 |issue= 45 |pages= 28563–7 |year= 1997 |pmid= 9353320 |doi=
*cite journal | author=Kim H, Baumann H |title=Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells. |journal=J. Biol. Chem. |volume=272 |issue= 49 |pages= 30741–7 |year= 1998 |pmid= 9388212 |doi=
*cite journal | author=Bravo J, Staunton D, Heath JK, Jones EY |title=Crystal structure of a cytokine-binding region of gp130. |journal=EMBO J. |volume=17 |issue= 6 |pages= 1665–74 |year= 1998 |pmid= 9501088 |doi= 10.1093/emboj/17.6.1665
*cite journal | author=Barton VA, Hudson KR, Heath JK |title=Identification of three distinct receptor binding sites of murine interleukin-11. |journal=J. Biol. Chem. |volume=274 |issue= 9 |pages= 5755–61 |year= 1999 |pmid= 10026196 |doi=
*cite journal | author=Hirota H, Chen J, Betz UA, "et al." |title=Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. |journal=Cell |volume=97 |issue= 2 |pages= 189–98 |year= 1999 |pmid= 10219240 |doi=
*cite journal | author=Tacken I, Dahmen H, Boisteau O, "et al." |title=Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis. |journal=Eur. J. Biochem. |volume=265 |issue= 2 |pages= 645–55 |year= 1999 |pmid= 10504396 |doi=
*cite journal | author=Chung TD, Yu JJ, Kong TA, "et al." |title=Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines. |journal=Prostate |volume=42 |issue= 1 |pages= 1–7 |year= 2000 |pmid= 10579793 |doi=

External links

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