Common gamma chain
Encyclopedia
The common gamma chain (γc) (or CD132), also known as interleukin-2 receptor subunit gamma or IL-2RG, is a cytokine receptor
sub-unit that is common to the receptor complexes for at least six different interleukin receptors: IL-2, IL-4
, IL-7
, IL-9
, IL-15
and interleukin-21 receptor
. The γc glycoprotein
is a member of the type I cytokine receptor
family expressed on most lymphocyte
(white blood cell) populations, and its gene is found on the X-chromosome of mammals.
This protein is located on the surface of immature blood-forming cells in bone marrow
. One end of the protein resides outside of the cell where it binds to cytokine
s and the other end of the protein resides in the interior of the cell where it transmits signals to the cell's nucleus. The common gamma chain partners with other proteins to direct blood-forming cells to form lymphocyte
s (a type of white blood cell). The receptor also directs the growth and maturation of lymphocyte subtypes: T cell
s, B cell
s, and natural killer cell
s. These cells kill viruses, make antibodies, and help regulate the entire immune system.
that in humans is encoded by the IL2RG gene
. The human IL2RG gene is located on the long (q) arm of the X chromosome
at position 13.1, from base pair
70,110,279 to base pair 70,114,423.
that contains extracellular, transmembrane, and intracellular domains.
from one cell to another and direct programs of cellular differentiation
.
-specific receptors to direct lymphocytes to respond to cytokine
s including IL-2
, IL-4
, IL-7
, IL-9
, IL-15
and IL-21
.
with Janus kinase 3
.
ation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15, T-cell and NK cell populations respectively fail to develop.
Experiments in animal models has shown X-SCID to occur similarly in dogs, but not in mice.
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...
sub-unit that is common to the receptor complexes for at least six different interleukin receptors: IL-2, IL-4
Interleukin-4 receptor
Interleukin 4 receptor is a type I cytokine receptor. IL4R is its human gene.-Interactions:Interleukin-4 receptor has been shown to interact with SHC1.-Further reading:-External links:...
, IL-7
Interleukin-7 receptor
The interleukin-7 receptor is a protein found on the surface of cells. It is made up of two different smaller protein chains - i.e. it is a heterodimer, and consists of two subunits, interleukin-7 receptor-α and common-γ chain receptor . The common-γ chain receptors is shared with various...
, IL-9
Interleukin-9 receptor
Interleukin 9 receptor also known as CD129 is a type I cytokine receptor. IL9R also denotes its human gene.-Interactions:Interleukin-9 receptor has been shown to interact with YWHAZ....
, IL-15
Interleukin-15 receptor
Interleukin-15 receptor is a type I cytokine receptor, binding interleukin-15. It consists of an interleukin 15 receptor, alpha subunit and shares common beta and gamma subunits with the IL-2 receptor....
and interleukin-21 receptor
Interleukin-21 receptor
Interleukin 21 receptor is a type I cytokine receptor. IL21R is its human gene.-Further reading:...
. The γc glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
is a member of the 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...
family expressed on most lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
(white blood cell) populations, and its gene is found on the X-chromosome of mammals.
This protein is located on the surface of immature blood-forming cells in bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. One end of the protein resides outside of the cell where it binds to 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...
s and the other end of the protein resides in the interior of the cell where it transmits signals to the cell's nucleus. The common gamma chain partners with other proteins to direct blood-forming cells to form lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s (a type of white blood cell). The receptor also directs the growth and maturation of lymphocyte subtypes: T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s, B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s, and natural killer cell
Natural killer cell
Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
s. These cells kill viruses, make antibodies, and help regulate the entire immune system.
Gene
Cytokine receptor common subunit gamma also known as interleukin-2 receptor subunit gamma or IL-2RG is a proteinProtein
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...
that in humans is encoded by the IL2RG gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. The human IL2RG gene is located on the long (q) arm of the X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
at position 13.1, from base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
70,110,279 to base pair 70,114,423.
Structure
The γc chain is an integral membrane proteinIntegral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
that contains extracellular, transmembrane, and intracellular domains.
Function
Lymphocytes expressing the common gamma chain can form functional receptors for these cytokine proteins, which transmit signalsCell 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...
from one cell to another and direct programs of cellular differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
.
Ligands
The γc chain partners with other ligandLigand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
-specific receptors to direct lymphocytes to respond to 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...
s including IL-2
Interleukin 2
Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
, IL-4
Interleukin 4
Interleukin-4, abbreviated IL-4, is a cytokine that induces differentiation of naive helper T cells to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent...
, IL-7
Interleukin 7
IL-7 a hematopoietic growth factor secreted by stromal cells in the red marrow and thymus. It is also produced by keratinocytes, dendritic cells, hepatocytes, neurons, and epithelial cells but is not produced by lymphocytes.- Genetics :...
, IL-9
Interleukin 9
Interleukin 9, also known as IL9, is a cytokine belonging to the group of interleukins.-Further reading:...
, IL-15
Interleukin 15
Interleukin 15 is a cytokine with structural similarity to IL-2. Like IL-2, IL-15 binds to and signals through the IL-2/IL-15 beta chain and the common gamma chain . IL-15 is secreted by mononuclear phagocytes following infection by virus...
and IL-21
Interleukin 21
Interleukin-21 is a protein that in humans is encoded by the IL21 gene.Interleukin 21 is a cytokine that has potent regulatory effects on cells of the immune system, including natural killer cells and cytotoxic T cells that can destroy virally infected or cancerous cells...
.
Signalling
IL2RG 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 Janus kinase 3
Janus kinase 3
Tyrosine-protein kinase JAK3 is an enzyme that in humans is encoded by the JAK3 gene.Since JAK3 expression is restricted mostly to hematopoietic cells, its role in cytokine signaling is thought to be more restricted than other JAKs. It is most commonly expressed in T cells and NK cells, but has...
.
X-linked severe combined immunodeficiency
X-linked severe combined immunodeficiency is caused by mutations in the IL2RG gene . More than 200 different mutations in the IL2RG gene have been identified in people with X-linked severe combined immunodeficiency (SCID) . Most of these mutations involve changes in one or a few DNA building blocks (nucleotides) in the gene. These changes lead to the production of a nonfunctional version of the common gamma chain protein or no production of protein. Without the common gamma chain, important chemical signals are not relayed to the nucleus and lymphocytes cannot develop normally. A lack of functional mature lymphocytes disrupts the immune system's ability to protect the body from infection. Sufferers have no functional immunity and can die within months after birth without successful bone marrow transplantBone marrow transplant
Hematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...
ation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15, T-cell and NK cell populations respectively fail to develop.
Experiments in animal models has shown X-SCID to occur similarly in dogs, but not in mice.