The interleukin 4 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 c ...

. IL4R is its human

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Function

This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind

interleukin 4 The interleukin 4 (IL4, IL-4) is a cytokine that induces differentiation of naive helper T cells ( Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 ...

and

interleukin 13 Interleukin 13 (IL-13) is a protein that in humans is encoded by the ''IL13'' gene. IL-13 was first cloned in 1993 and is located on chromosome 5q31 with a length of 1.4kb. It has a mass of 13 kDa and folds into 4 alpha helical bundles. The second ...

to regulate

IgE Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (ε chain) and two light chains, with the ε c ...

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

production in B cells. Among

T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells 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 re ...

, the encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by an alternate splice variant or by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitis, asthma, or eczema. Two transcript variants encoding different isoforms, a membrane-bound and a soluble form, have been found for this gene. Interactions of IL-4 with TNFα promote structural changes to vascular endothelial cells, thus playing an important role in tissue inflammation. The binding of IL-4 or IL-13 to the IL-4 receptor on the surface of

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

results in the alternative activation of those macrophages. Alternatively activated macrophages (AAMΦ) downregulate inflammatory mediators such as

IFNγ Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...

during immune responses, particularly with regards to helminth infections. IL4 signalling also determines the levels of CD20 on normal and malignant B cells by activation the transcription factor STAT6.

Interactions

Interleukin-4 receptor has been shown to interact with

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 Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of pro ...

Structure

The N-terminal (

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

) portion of interleukin-4 receptor is related in overall topology to

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

type III modules and folds into a sandwich comprising seven antiparallel

beta sheets The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

arranged in a three-strand and a four-strand beta-pleated sheet. They are required for binding of interleukin-4 to the receptor alpha chain, which is a crucial event for the generation of a Th2-dominated early

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

References

External links

*
PDBe-KB
provides an overview of all the structure information available in the PDB for Human Interleukin-4 receptor subunit alpha {{InterPro content, IPR015319 Type I cytokine receptors Clusters of differentiation Protein domains

Function

Interactions

Structure

See also

References

Further reading

External links