Glycoprotein 130
Encyclopedia
Glycoprotein 130 is a transmembrane protein
which is the founding member of the class of all cytokine receptor
s. It forms one subunit
of type I cytokine receptor
s 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 kinase
s to elicit an intracellular signal
following receptor interaction with its ligand. Structurally, gp130 is composed of five fibronectin
type-III domain
s and one immunoglobulin-like C2-type (immunoglobulin-like) domain in its extracellular portion.
ic 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.
mice who are born show a number of defects including impaired development of the ventricular
myocardium. Haematopoietic
effects included reduced numbers of stem cell
s in the spleen
and liver
.
activity. Instead, it is phosphorylated
on tyrosine
residues after complexing
with other protein
s. The phosphorylation leads to association with JAK
/Tyk tyrosine kinases and STAT protein
transcription factor
s. In particular, STAT-3 is activated which leads to the activation of many downstream genes. Other pathways activated include RAS and MAPK signaling.
with TLE1
, SOCS3
, HER2/neu
, PTPN11
, Leukemia inhibitory factor receptor
, Grb2
, Janus kinase 1
and SHC1
.
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
which is the founding member of the class of all cytokine receptor
Cytokine receptor
Cytokine receptors are receptors that bind cytokines.In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors has now been...
s. It forms one subunit
Protein subunit
In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...
of type I cytokine receptor
Type I cytokine receptor
Type I cytokine receptors are transmembrane receptors expressed on the surface of cells that recognize and respond to cytokines with four α-helical strands. These receptors are also known under the name hemopoietin receptors, and share a common amino acid motif in the extracellular portion...
s within the IL-6 receptor family. It is often referred to as the common gp130 subunit, and is important for signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
following cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
engagement. As with other type I cytokine receptors, gp130 possesses a WSXWS amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
motif that ensures correct protein folding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
and ligand
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
binding. It interacts with Janus kinase
Janus kinase
Janus kinase is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 & 2 , but were ultimately published as "Janus kinase"...
s to elicit an intracellular signal
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
following receptor interaction with its ligand. Structurally, gp130 is composed of five fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
type-III domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
s and one 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 homodimerizes to form a hexamerHexamer
A hexamer is a thing composed out of six sub-units.In microbiology, a hexamer is one of the proteins composing the polyhedral protein shell that encloses the bacterial micro-compartments known as carboxysomes....
ic complex which can produce downstream signals. There are many other proteins which associate with gp130, such as cardiotrophin 1
Cardiotrophin 1
Cardiotrophin-1 is a cytokine. It is a cardiac hypertrophic factor of 21.5 kDa and a protein member of the IL-6 cytokine family. CT-1 is associated with the pathophysiology of heart diseases, including hypertension, myocardial infarction, valvular heart disease, and congestive heart failure...
(CT-1), leukemia inhibitory factor
Leukemia inhibitory factor
Leukemia inhibitory factor, or LIF, an interleukin 6 class cytokine, is a protein in cells that affects cell growth and development.-Function:LIF derives its name from its ability to induce the terminal differentiation of myeloid leukemic cells...
(LIF), ciliary neurotrophic factor
Ciliary neurotrophic factor
Ciliary neurotrophic factor is a protein that in humans is encoded by the CNTF gene.CNTF has also been shown to be expressed by cells on the bone surface, and to reduce the activity of bone forming cells, osteoblasts.- Satiety effects :...
(CNTF), oncostatin M
Oncostatin M
Oncostatin M, also known as OSM, is a protein that in humans is encoded by the OSM gene.OSM is a pleiotropic cytokine that belongs to the interleukin 6 group of cytokines. Of these cytokines it most closely resembles leukemia inhibitory factor in both structure and function...
(OSM), and IL-11
Interleukin 11
Interleukin 11 is a protein that in humans is encoded by the IL11 gene.IL-11 is a multifunctional cytokine first isolated in 1990 from bone marrow-derived stromal cells. It is a key regulator of multiple events in hematopoiesis, most notably the stimulation of megakaryocyte maturation...
. 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. HomozygousZygosity
Zygosity refers to the similarity of alleles for a trait in an organism. If both alleles are the same, the organism is homozygous for the trait. If both alleles are different, the organism is heterozygous for that trait...
mice who are born show a number of defects including impaired development of the ventricular
Ventricle (heart)
In the heart, a ventricle is one of two large chambers that collect and expel blood received from an atrium towards the peripheral beds within the body and lungs. The Atria primes the Pump...
myocardium. Haematopoietic
Haematopoiesis
Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells...
effects included reduced numbers of stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s in the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
and liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
.
Signal transduction
gp130 has no intrinsic tyrosine kinaseTyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
activity. Instead, it is phosphorylated
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
on tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
residues after complexing
Protein complex
A multiprotein complex is a group of two or more associated polypeptide chains. If the different polypeptide chains contain different protein domain, the resulting multiprotein complex can have multiple catalytic functions...
with other protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. The phosphorylation leads to association with JAK
Janus kinase
Janus kinase is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 & 2 , but were ultimately published as "Janus kinase"...
/Tyk tyrosine kinases and STAT protein
STAT protein
The STAT protein regulates many aspects of growth, survival and differentiation in cells...
transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s. In particular, STAT-3 is activated which leads to the activation of many downstream genes. Other pathways activated include RAS and MAPK signaling.
Interactions
Glycoprotein 130 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with TLE1
TLE1
Transducin-like enhancer protein 1 is a protein that in humans is encoded by the TLE1 gene.-Interactions:TLE1 has been shown to interact with TLE2, Glycoprotein 130, UTY, HES6, RUNX3, SIX3 and RUNX1.-Further reading:...
, SOCS3
SOCS3
Suppressor of cytokine signaling 3 is a protein that in humans is encoded by the SOCS3 gene.-Interactions:SOCS3 has been shown to interact with PTPN11, Glycoprotein 130, Erythropoietin receptor, Janus kinase 2, RAS p21 protein activator 1 and Insulin-like growth factor 1 receptor.-Regulation:There...
, HER2/neu
HER2/neu
HER-2 also known as proto-oncogene Neu, receptor tyrosine-protein kinase erbB-2, CD340 or p185 is an enzyme that in humans is encoded by the ERBB2 gene. Over expression of this gene is correlated with higher aggressiveness in breast cancers...
, PTPN11
PTPN11
Tyrosine-protein phosphatase non-receptor type 11 also known as protein-tyrosine phosphatase 1D or protein-tyrosine phosphatase 2C is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase Shp2.PTPN11 is a member of the protein tyrosine phosphatase ...
, Leukemia inhibitory factor receptor
Leukemia inhibitory factor receptor
LIFR also known as CD118 , is a subunit of a receptor for leukemia inhibitory factor.-Interactions:Leukemia inhibitory factor receptor has been shown to interact with Glycoprotein 130....
, Grb2
Grb2
Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....
, Janus kinase 1
Janus kinase 1
JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain of type I cytokine receptors, to elicit signals from the IL-2 receptor family , the IL-4 receptor family , the gp130 receptor family JAK1 is a human...
and SHC1
SHC1
SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene. SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells....
.