Glycoprotein 130

Glycoprotein 130 (also known as gp130, IL6ST, IL6-beta or CD130) is a is_associated_with::transmembrane protein which is the founding member of the class of all is_associated_with::cytokine receptors. It forms one subunit of the is_associated_with::type I cytokine receptor within the is_associated_with::IL-6 receptor family. It is often referred to as the common gp130 subunit, and is important for is_associated_with::signal transduction following is_associated_with::cytokine engagement. As with other type I cytokine receptors, gp130 possesses a WSXWS is_associated_with::amino acid motif that ensures correct is_associated_with::protein folding and ligand binding. It interacts with is_associated_with::Janus kinases to elicit an intracellular signal following receptor interaction with its ligand. Structurally, gp130 is composed of five is_associated_with::fibronectin type-III domains and one is_associated_with::immunoglobulin-like C2-type (immunoglobulin-like) domain in its extracellular portion.

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 is_associated_with::homodimerizes to form a is_associated_with::hexameric complex which can produce downstream signals. There are many other proteins which associate with gp130, such as is_associated_with::cardiotrophin 1 (CT-1), is_associated_with::leukemia inhibitory factor (LIF), is_associated_with::ciliary neurotrophic factor (CNTF), is_associated_with::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 is_associated_with::LIF-R, is_associated_with::OSM-R, and is_associated_with::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 is_associated_with::myocardium. Haematopoietic effects included reduced numbers of is_associated_with::stem cells in the is_associated_with::spleen and is_associated_with::liver.

Signal transduction
gp130 has no intrinsic is_associated_with::tyrosine kinase activity. Instead, it is phosphorylated on is_associated_with::tyrosine residues after complexing with other is_associated_with::proteins. The phosphorylation leads to association with JAK/Tyk tyrosine kinases and is_associated_with::STAT protein is_associated_with::transcription factors. In particular, is_associated_with::STAT-3 is activated which leads to the activation of many downstream genes. Other pathways activated include RAS and is_associated_with::MAPK signaling.

Interactions
Glycoprotein 130 has been shown to interact with:
 * is_associated_with::Grb2,
 * is_associated_with::HER2/neu,
 * is_associated_with::Janus kinase 1
 * is_associated_with::Leukemia inhibitory factor receptor,
 * is_associated_with::PTPN11,
 * is_associated_with::SHC1,
 * is_associated_with::SOCS3, and
 * is_associated_with::TLE1.