The common gamma chain (γ
c) (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
The Ilyushin Il-2 (Russian language, Russian: Илью́шин Ил-2) is a Ground attack aircraft, ground-attack plane that was produced by the Soviet Union in large numbers during the World War II, Second World War. The word ''shturmovík'' (C ...
,
IL-4,
IL-7,
IL-9,
IL-15 and
interleukin-21 receptor. The γ
c glycoprotein
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
is a member of the
type I cytokine receptor family expressed on most
lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...
(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 is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
. One end of the protein resides outside the cell where it binds to
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
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
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...
s (a type of white blood cell). The receptor also directs the growth and maturation of lymphocyte subtypes:
T cell
T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
s,
B cell
B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...
s,
innate lymphoid cells, and
natural killer cell
Natural killer cells, also known as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. They are a kind of large granular lymphocytes (LGL), and belong to the rapidly expanding family of known innate lymphoid cells ...
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
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''IL2RG''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
The human IL2RG gene is located on the long (q) arm of the
X chromosome
The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...
at position 13.1, from
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
70,110,279 to base pair 70,114,423.
Structure
The γ
c chain is an
integral membrane protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comp ...
that contains extracellular, transmembrane, and intracellular domains.
Function
Lymphocytes expressing the common gamma chain can form functional receptors for these cytokine proteins, which transmit
signals
A signal is both the process and the result of Signal transmission, transmission of data over some transmission media, media accomplished by embedding some variation. Signals are important in multiple subject fields including signal processin ...
from one cell to another and direct programs of
cellular differentiation
Cellular differentiation is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellula ...
.
Ligands
The γ
c chain partners with other
ligand
In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
-specific receptors to direct lymphocytes to respond to
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s including
IL-2
The Ilyushin Il-2 (Russian language, Russian: Илью́шин Ил-2) is a Ground attack aircraft, ground-attack plane that was produced by the Soviet Union in large numbers during the World War II, Second World War. The word ''shturmovík'' (C ...
,
IL-4,
IL-7,
IL-9,
IL-15 and
IL-21.
Signaling
IL2RG has been shown to
interact with
Janus kinase 3.
IL2RG plays a critical role in lymphocyte signal transduction in response to
IL-4,
IL-7,
IL-9,
IL-21,
IL-15, and
IL-2
The Ilyushin Il-2 (Russian language, Russian: Илью́шин Ил-2) is a Ground attack aircraft, ground-attack plane that was produced by the Soviet Union in large numbers during the World War II, Second World War. The word ''shturmovík'' (C ...
. Once either
IL4-Rα,
IL-7Rα,
IL-9Rα,
IL-21Rα,
IL-2R or
IL-15R has bound to their respective ligands, IL2RG is quickly recruited and forms a
heterodimer
In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...
with the cytoplasmic tail of the opposing receptor. After the heterodimer has formed, IL2RG then activates
JAK3, and the opposing receptor activates
JAK1. JAK1 and JAK3 then
phosphorylate
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writt ...
both IL2RG and the opposing receptor's cytoplasmic tail. This phosphorylation allows for IL-2RG and its opposing receptor to recruit a
STAT protein. JAK3 and JAK1 subsequently phosphorylate the recruited STAT, allowing the STAT to form a dimer or
tetramer
A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula ...
with other phosphorylated STAT proteins. Finally, these dimer or STATs translocate to the nucleus, bind STAT motifs within the nuclear DNA, and induce transcription within specific genes.
Clinical significance
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
nucleotides
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
(DNA building blocks) 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. Affected people have no functional immunity and can die within months after birth without successful
bone marrow transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce a ...
ation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15,
T-cell
T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...
and
NK cell populations respectively fail to develop.
Experiments in animal models have shown X-SCID to occur similarly in dogs, but not in mice.
Schizophrenia
Alterations in the immune response are involved in
pathogenesis
In pathology, pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes .
Descript ...
of many neuropsychiatric disorders including
schizophrenia
Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
. Distinct gene variants of a number of pro-inflammatory and chemotactic cytokines together with their receptors associate with this disorder. IL2RG represents an important signaling component of many interleukin receptors and so far, no data on the functional state of this receptor in schizophrenia have been reported. Over-expression of the IL2RG gene may be implicated in altered immune response in schizophrenia and contribute to the pathogenesis of this disorder.
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
External links
*
*
{{DEFAULTSORT:Common Gamma Chain
Type I cytokine receptors
Immune system