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 and CSF2RB. The IL-5 receptor (IL-5R) belongs to the

family and is a heterodimer composed of two

polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...

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 biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

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. They are the largest type of granulocyte. They are responsible for inflammatory reactio ...

and murine B1 cells or B cell precursors. Like many other cytokine receptors,

alternative splicing Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...

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 discoverie ...

( JAK) 2, a protein tyrosine-kinase 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 (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

. In fact, the β-subunit of the IL-5 receptor is also found in IL-3 and GM-CSF 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 The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell and ...

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 ...

, as well as

LYN Lyn or LYN may refer to: People * Lyn (singer), South Korean singer * Lyn (gamer), South Korean ''Warcraft III'' player * Lyn (given name) * Lyn (surname) In science and technology * Lynx (constellation), standard abbreviation * Lyn (locomotive ...

, 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 directed against the alpha chain of the interleukin-5 receptor ( CD125). It was developed by MedImmune for the treatment of asthma. It is currently marketed by Astrazen ...

binds to IL-5Ra, while

mepolizumab Mepolizumab, sold under the brand name Nucala by GlaxoSmithKline, is a humanized monoclonal antibody used for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome (HES). It r ...

and

reslizumab Reslizumab, sold under the brand names Cinqair and Cinqaero, is a humanized monoclonal antibody against human Interleukin 5, interleukin-5 (IL-5). Reslizumab binds specifically to IL-5, a key cytokine responsible for the differentiation, maturati ...

bind to IL-5, preventing it from binding to IL-5Ra.

References

External links

* {{Interleukin receptor modulators Type I cytokine receptors