Cytokine Receptors

Cytokines are proteins that coordinate the activity of the immune system. Many cytokines belong to a family exhibiting a four-helical topology. Receptors for these cytokines belong to the immunoglobulin superfamily and are all type I transmembrane proteins.

Keywords: cytokine-binding; immunoglobulin superfamily; JAK-STAT-signalling; shedding; alternative splicing

Figure 1. Cell surface receptor complex formation of cytokines. Binding of growth hormone (GH), granulocyte–macrophage colony-stimulating factor (GM-CSF) and ciliary neurotrophic factor (CNTF) to their cell surface receptors. (a) GH binds to a homodimer of the GH receptor. (b) GM-CSF first binds to the GM-CSF receptor. This complex then binds to the subunit of the IL-3 receptor. (c) NTF first binds to the CNTF receptor. This complex thereupon associates with a heterodimer of gp130 and LIF receptor.
Figure 2. Signal transduction of cytokines. Dimerization of signal-transducing cytokine receptor subunits leads to Janus kinase (JAK) activation. The activated JAK phosphorylates the cytoplasmic portion of the cytokine receptor. This leads to signal transducer and activator of transcription (STAT) recruitment via phosphotyrosine, recognizing src homology-2 (SH2) domains. Phosphorylated STAT factors dimerize and translocate to the cell nucleus where STAT factors act as transcription factors leading to the transcriptional activation of target genes.
Figure 3. Possible consequences of soluble receptor formation. (a) Inhibition of cytokine signalling by soluble receptors. Soluble receptors compete with membrane-bound receptors for the ligand. A molar excess of soluble receptor leads to an inhibition of the cytokine response. (b) Activation of target cells by transsignalling via soluble cytokine receptors. Some cytokine receptors can bind their cognate ligands and thereafter bind to transducing subunits, thereby inducing signal transduction.
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 References
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 Further Reading
    Chen E, Gadina M, Chen M and O'Shea JJ (1999) Advances in cytokine signaling: the role of Jaks and Stats. Transplantation Proceedings 31: 1482–1487.
    Müllberg J, Althoff K, Jostock T and Rose-John S (2000) The importance of shedding of membrane proteins for cytokine biology. European Cytokine Network 11: 27–38.
    Pawson T and Nash P (2000) Protein–protein interactions define specificity in signal transduction. Genes and Development 14: 1027–1047.
    Peters M, Müller A and Rose-John S (1998) Interleukin-6 and soluble interleukin-6 receptor: direct stimulation of gp130 and hematopoiesis. Blood 92: 3495–3504.
    Shirogane T, Fukada T, Muller JM et al. (1999) Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis. Immunity 11: 709–719.
    Sprang SR and Bazan JF (1993) Cytokine structural taxonomy and mechanism of receptor engagement. Current Opinion in Structural Biology 3: 815–827.
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Rose‐John, Stefan(Sep 2005) Cytokine Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003979]