Cytokine receptor

Key steps of the JAK-STAT pathway for type 1 and 2 cytokine receptors

Signal transduction. (Cytokine receptor at center left.)

Cytokine receptors are receptors that bind to 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 directly linked to certain debilitating immunodeficiency states. In this regard, and also because the redundancy and pleiotropy of cytokines are a consequence of their homologous receptors, many authorities are now of the opinion that a classification of cytokine receptors would be more clinically and experimentally useful.

Classification

A classification of cytokine receptors based on their three-dimensional structure has been attempted. (Such a classification, though seemingly cumbersome, provides several unique perspectives for attractive pharmacotherapeutic targets.)

• Type I cytokine receptors, whose members have certain conserved motifs in their extracellular amino-acid domain. The IL-2 receptor belongs to this chain, whose γ-chain (common to several other cytokines) deficiency is directly responsible for the x-linked form of Severe Combined Immunodeficiency (X-SCID).
• Type II cytokine receptors, whose members are receptors mainly for interferons.
• Immunoglobulin (Ig) superfamily, which are ubiquitously present throughout several cells and tissues of the vertebrate body
• Tumor necrosis factor receptor family, whose members share a cysteine-rich common extracellular binding domain, and includes several other non-cytokine ligands like receptors, CD40, CD27 and CD30, besides the ligands on which the family is named (TNF).
• Chemokine receptors, two of which acting as binding proteins for HIV (CXCR4 and CCR5). They are G protein coupled receptors.
• TGF-beta receptor family, which are Serine/threonine kinase receptors. Includes the TGF beta receptors

Comparison

Type	Examples	Structure	Mechanism
type I cytokine receptor	Type 1 interleukin receptors Erythropoietin receptor GM-CSF receptor G-CSF receptor growth hormone receptor prolactin receptor Oncostatin M receptor Leukemia inhibitory factor receptor	Certain conserved motifs in their extracellular amino-acid domain. Connected to Janus kinase (JAK) family of tyrosine kinases. Many have a FN-III superfamily domain and an immunoglobulin-like fold.	JAK phosphorylate and activate downstream proteins involved in their signal transduction pathways
type II cytokine receptor	Type II interleukin receptors interferon-alpha/beta receptor interferon-gamma receptor
Many members of the immunoglobulin superfamily	Interleukin-1 receptor CSF1 C-kit receptor Interleukin-18 receptor	Share structural homology with immunoglobulins (antibodies), cell adhesion molecules, and even some cytokine. Includes with the two classes above.
Tumor necrosis factor receptor family	CD27 CD30 CD40 CD120 Lymphotoxin beta receptor	cysteine-rich common extracellular binding domain
chemokine receptors	Interleukin-8 receptor CCR1 CXCR4 MCAF receptor NAP-2 receptor	Seven transmembrane helix, rhodopsin-like receptor	G protein-coupled
TGF-beta receptor family	TGF beta receptor 1 TGF beta receptor 2	Serine/threonine kinase receptors	Dimeric TGFBR2 binds to TGFB and phosphorylates TGFBR1, which phosphorylates the SMADs. See TGF beta signaling pathway.

Solubility

Cytokine receptors may be both membrane-bound and soluble. Soluble cytokine receptors are extremely common regulators of cytokine function. Soluble cytokine receptors typically consist of the extracellular portions of membrane-bound receptors. .

See also

• STAT protein

External links

• Cytokine-cytokine receptor interaction map from KEGG
• Cytokine+receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)