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Cytokine receptors are
receptorIn biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s that bind
cytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s.
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, in fact, 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 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 common amino acid motif in the extracellular portion...
s, 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 ImmunodeficiencySevere combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
(X-SCIDX-linked severe combined immunodeficiency is an immunodeficiency disorder that affects lymphocytes. It is a recessive trait stemming from a defective version of the gene responsible for the functionality of the Interleukin 2 receptor ....
).
- Type II cytokine receptor
Type II cytokine receptors are transmembrane proteins that are expressed on the surface of certain cells, which bind and respond to a select group of cytokines...
s, whose members are receptors mainly for interferonInterferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
s.
- Immunoglobulin (Ig) superfamily
The immunoglobulin superfamily is a large group of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins ; they all possess a...
, which are ubiquitously present throughout several cells and tissues of the vertebrate body
- Tumor necrosis factor receptor family, whose members share a cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
-rich common extracellular binding domain, and includes several other non-cytokine ligands like CD40, CD27CD27 is a tumor necrosis factor receptor.-Interactions:CD27 has been shown to interact with SIVA1, TRAF2 and TRAF3.-External links:...
and CD30CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and tumor marker.This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, and mediate the signal transduction that leads to the...
, besides the ligands on which the family is named (TNF).
- Chemokine receptor
Chemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. There have been 19 distinct chemokine receptors described in mammals...
s, two of which acting as binding proteins for HIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
(CXCR4C-X-C chemokine receptor type 4 also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene.- Function :...
and CCR5C-C chemokine receptor type 5, also known as CCR5, is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins...
). They are G protein coupled receptors.
- TGF beta receptors
TGFβ receptors are single pass serine/threonine kinase receptors. They exist in several different isoforms that can be homo- or heterodimeric...
Comparison
| Type | Examples | Structure | Mechanism |
| 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 common amino acid motif in the extracellular portion...
|
- Type 1 interleukin receptors
- Erythropoietin receptor
The erythropoietin receptor is a protein that in humans is encoded by the EPOR gene. EpoR is a 59 kDa peptide and is a member of the cytokine receptor family. EpoR pre-exists as dimers...
- GM-CSF receptor
- G-CSF receptor
- growth hormone receptor
Growth hormone receptor is a protein that in humans is encoded by the GHR gene. GHR orthologs have been identified in most mammals.-Interactions:...
- prolactin receptor
The prolactin receptor—encoded by a gene on Chromosome 5p13-14—interacts with the prolactin molecule as a transmembrane receptor.Thus it contains an extracellular region that binds prolactin, a transmembrane regions, and a cytoplasmatic region....
- Oncostatin M receptor
Oncostatin-M specific receptor subunit beta also known as the oncostatin M receptor, is one of the receptor proteins for oncostatin M, that in humans is encoded by the OSMR gene.OSMR is a member of the type I cytokine receptor family...
- Leukemia inhibitory factor receptor
LIFR also known as CD118 , is a subunit of a receptor for leukemia inhibitory factor.-Interactions:Leukemia inhibitory factor receptor has been shown to interact with Glycoprotein 130....
|
Certain conserved motifs in their extracellular amino-acid domain. Connected to Janus kinaseJanus kinase 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 & 2 , but were ultimately published as "Janus kinase"...
(JAK) family of tyrosine kinaseA tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
s |
JAK phosphorylate and activate downstream proteins involved in their signal transductionSignal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
pathways |
| type II cytokine receptor Type II cytokine receptors are transmembrane proteins that are expressed on the surface of certain cells, which bind and respond to a select group of cytokines...
|
Type II interleukin receptors
interferon-alpha/beta receptor The interferon-α/β receptor is a receptor which binds type I interferons including interferon-α and -β. It is a heteromeric receptor composed of one chain with two subunits referred to as IFNAR1 and IFNAR2. It is a cell surface receptor. Binding of cytokine follows a JAK-STAT signaling pathway...
interferon-gamma receptorThe interferon-gamma receptor is a receptor which binds interferon-γ, the sole member of interferon type II.- Structure and function :...
|
| Many members of the immunoglobulin superfamily The immunoglobulin superfamily is a large group of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins ; they all possess a...
|
Interleukin-1 receptor Interleukin-1 receptor is a cytokine receptor which binds interleukin 1. Two forms of the receptor exist. The type I receptor is primarily responsible for transmitting the inflammatory effects of interleukin-1 while type II receptors may act as a suppressor of IL-1 activity by competing for...
CSF1Colony stimulating factor 1 receptor , also known as macrophage colony-stimulating factor receptor , and CD115 , is a cell-surface protein encoded, in humans, by the CSF1R gene...
C-kit receptorMast/stem cell growth factor receptor also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117 is a protein that in humans is encoded by the KIT gene...
Interleukin-18 receptorThe interleukin-18 receptor is an interleukin receptor of the immunoglobulin superfamily. IL-18R is a heteromeric complex of alpha- and beta-chains encoded by the genes and respectively....
|
Share structural homology Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
with immunoglobulins (antibodiesAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
), cell adhesion moleculeCell Adhesion Molecules are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix in the process called cell adhesion....
s, and even some cytokines. |
| Tumor necrosis factor receptor family |
CD27 CD27 is a tumor necrosis factor receptor.-Interactions:CD27 has been shown to interact with SIVA1, TRAF2 and TRAF3.-External links:...
CD30CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and tumor marker.This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, and mediate the signal transduction that leads to the...
CD40
CD120CD120 , also known as the tumor necrosis factor receptor . This protein is a member of the tumor necrosis factor receptor superfamily.- Receptor subtypes :...
Lymphotoxin beta receptorLymphotoxin beta receptor is a receptor for lymphotoxin which in humans is encoded by the LTBR gene.-Function:The protein encoded by this gene is a member of the tumor necrosis factor family of receptors. It is expressed on the surface of most cell types, including cells of epithelial and myeloid...
|
cysteineCysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
-rich common extracellular binding domain |
| chemokine receptor Chemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. There have been 19 distinct chemokine receptors described in mammals...
s |
Interleukin-8 receptor Interleukin-8 receptor is an interleukin receptor of the chemokine receptor type....
CCR1C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.CCR1 has also recently been designated CD191 .-External links:...
CXCR4C-X-C chemokine receptor type 4 also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene.- Function :...
MCAF receptor
NAP-2 receptor |
Seven transmembrane helix |
G proteinG proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
-coupled |
| TGF beta receptors TGFβ receptors are single pass serine/threonine kinase receptors. They exist in several different isoforms that can be homo- or heterodimeric...
|
TGF beta receptor 1 Transforming growth factor, beta receptor I is a TGF beta receptor. TGFBR1 is its human gene.-Interactions:...
TGF beta receptor 2Transforming growth factor, beta receptor II is a TGF beta receptor. TGFBR2 is its human gene.It is a tumor suppressor gene.-Interactions:...
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Solubility
Cytokine receptors may be both membrane-bound and soluble.
Soluble cytokine receptors are extremely common regulators of
cytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
function.