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 cytokines[1].


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.




Contents






  • 1 Classification


  • 2 Comparison


  • 3 Solubility


  • 4 See also


  • 5 References


  • 6 External links





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[2]

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. .[3]



See also


  • STAT protein


References





  1. ^ Brooks, Andrew J.; Dehkhoda, Farhad; Kragelund, Birthe B. (2017). "Cytokine Receptors". Principles of Endocrinology and Hormone Action. Springer International Publishing. pp. 1–29. doi:10.1007/978-3-319-27318-1_8-2. ISBN 9783319273181..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{quotes:"""""""'""'"}.mw-parser-output .citation .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-limited a,.mw-parser-output .citation .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/4/4c/Wikisource-logo.svg/12px-Wikisource-logo.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-maint{display:none;color:#33aa33;margin-left:0.3em}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}


  2. ^ Arimont A, Sun S, Smit MJ, Leurs R, de Esch IJ, de Graaf C (2017). "Structural Analysis of Chemokine Receptor-Ligand Interactions". J Med Chem. 60 (12): 4735–4779. doi:10.1021/acs.jmedchem.6b01309. PMC 5483895. PMID 28165741.


  3. ^ Heaney ML1, Golde DW (1998). "Soluble receptors in human disease". Journal of Leukocyte Biology. 64 (2): 135–146. PMID 9715251.




External links




  • Cytokine-cytokine receptor interaction map from KEGG


  • Cytokine+receptors at the US National Library of Medicine Medical Subject Headings (MeSH)















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