The interleukin-5 receptor is a
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 ...
. It is a heterodimer of the
interleukin 5 receptor alpha subunit
Interleukin 5 receptor, alpha (IL5RA) also known as CD125 (Cluster of Differentiation 125) is a subunit of the Interleukin-5 receptor. IL5RA also denotes its human gene.
Function
The protein encoded by this gene is an interleukin 5 specific su ...
and
CSF2RB
CSF2RB (also known as cytokine receptor common subunit beta) is a common subunit to the following type I cytokine receptors:
* GM-CSF receptor
* IL-3 receptor
*IL-5 receptor
The interleukin-5 receptor is a type I cytokine receptor. It is a heter ...
.
The IL-5 receptor (IL-5R) belongs to the
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 ...
family and is a heterodimer composed of two
polypeptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
chains, one α subunit, which binds IL-5 and confers upon the receptor cytokine specificity, and one β subunit, which contains the
signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
domains.
α-subunit
The IL-5Rα chain is exclusively expressed by eosinophils, some
basophils
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammat ...
and murine B1 cells or B cell precursors.
Like many other cytokine receptors,
alternative splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
of the α-chain gene results in expression of either a membrane bound or soluble form of the bα-chain. The soluble form does not lead to signal transduction and therefore has an antagonistic effect on IL-5 signaling. Both monomeric forms of IL-5Rα are low affinity receptors, while dimerization with the β-chain produces a high affinity receptor.
In either case, the α-chain exclusively binds IL-5 and the intra-cellular portion of IL-5Rα is associated with
Janus kinase
Janus kinase (JAK) 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 and 2 (since they were just two of many discoveries ...
(
JAK
Jak may refer to:
Places
* Ják, a village in Hungary
People
* Jak Alnwick (born 1993), English football goalkeeper
* Jak Jones (born 1993), Welsh professional snooker player
* Raymond Jackson ("JAK") (1927–1997), UK cartoonist
* Jak Airport ( ...
) 2, a
protein tyrosine-kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
essential in IL-5 signal transduction.
β-subunit
The β-subunit of the IL-5 receptor is responsible for signal transduction and contains several intracellular signaling domains. Unlike the α-chain, the β-chain does not bind IL-5, is not specific to this cytokine, and is expressed on practically all
leukocytes
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
. In fact, the β-subunit of the IL-5 receptor is also found in
IL-3 and
GM-CSF
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that ...
receptors where it is associated with
IL-3Rα and
GM-CSFRα subunits respectively.
Therefore, it is known as the common β receptor or βc. As with the IL-5Rα subunit, the β subunit’s
cytoplasmic
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. Th ...
domain is constitutively associated with
JAK2
Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF rec ...
,
as well as
LYN,
another tyrosine kinase, which are both essential for IL-5 signal transduction.
Drug target
Three monoclonal antibodies are available to target IL-5R.
Benralizumab
Benralizumab, sold under the brand name Fasenra, is a monoclonal antibody medication which is developed by MedImmune for the treatment of asthma. It is directed against the alpha-chain of the interleukin-5 receptor ( CD125).
Two phase III clinica ...
binds to IL-5Ra, while
mepolizumab
Mepolizumab, sold under the brand name Nucala, is a humanized monoclonal antibody used for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis, and hypereosinophilic syndrome (HES). It recognizes and blocks interleukin-5 (IL ...
and
reslizumab
Reslizumab is a humanized monoclonal antibody against human interleukin-5 (IL-5). Reslizumab binds specifically to IL-5, a key cytokine responsible for the differentiation, maturation, recruitment and activation of human eosinophils. By binding t ...
bind to IL-5, preventing it from binding to IL-5Ra.
References
External links
*
{{Interleukin receptor modulators
Type I cytokine receptors