Cytokine receptors, characteristics

Recombinant DNA technology has also facilitated detailed study of cytokine receptors. Based upon amino acid sequence homology, receptors are usually classified as belonging to one of six known superfamilies (Table 8.3). Individual members of any one superfamily characteristically display 20-50 per cent homology. Conserved amino acids normally occur in discrete bands or clusters, which usually correspond to a discrete domain in the receptor. Most receptors exhibit multiple domains. In some cases a single receptor may contain domains characteristic of two or more superfamilies. For example, the IL-6 receptor contains domains characteristic of both the haematopoietic and immunoglobulin superfamilies, making it a member of both. 

In the extracellular region, cytokine receptors have characteristic sequence sections that specify the particular receptor type. Cys-rich domains, fibronectin type Ill-like domains and immimoglobulin-like domains can be differentiated. Cytokine receptors of type I often have a conserved WSXWS motif in the extracellular region. 

IL-IOR is a single-chain receptor. IL-IOR belongs to the class II cytokine receptor family that also includes the IFN receptors (IFNy and IFNap receptors). The extracellular region consists of two homologous fibronectin type III domains that are without the WSXWS motif characteristic of class I cytokine receptors. It is expressed on B cells, thymocytes, and other cellular lines such as mast cells and macrophages. Human IL-IOR mRNA is restricted mostly to hematopoietic cells and cell lines. ... 

In the extracellular region, cytokine receptors have characteristic sequence sections that specify the particular receptor type. Cys-rich domains, fibronectin-type IH-like domains and immunoglobulin-like domains can be differentiated, among others. Cytokine receptors of type I often have a conserved WSXWS motif in the extracellular region. With the exception of ciliary neurotrophic receptor, which is membrane-anchored via a GPI anchor (see Section 3.7.4), all receptors have a single transmembrane domain of 22 - 28 amino acids. Two motifs, called box 1 and box 2, are relatively conserved in the membrane-proximal part of the cytoplasmic domain. However, no known catalytic domain is found on the cytoplasmic part of the receptors. 

NK cells constitute only a small proportion of lymphoid cells (5 to 20%) (Andoniou et al., 2006). ffowever, their ability to respond to multiple ligands, as opposed to T cells which respond to only one antigen, allows a substantial number of NK cells to respond to a specific insult during the innate immune response. In addition, NK cells constitutively express cytokine receptors allowing them to respond rapidly (Yokoyama et al., 2004). These two characteristics allow for a robust response despite their relatively low numbers. 

In the absence of selective antagonists, cytokines have been classified either on the basis of common functional properties or on the stmctural characteristics of their receptors. 

Goldberg-Bittman L, Sagi-Assif O, Meshel T, et al. Cellular characteristics of neuroblastoma cells regulation by the ELR -CXC chemokine CXCL10 and expression of a CXCR3-like receptor. Cytokine 2005 29 105-117. 

The presence of at least two chains is the common characteristic of many of these receptors. The cytokines having two chain structures exhibit dual affinity although there are some exceptions. The examples of receptors with two chain structures include sharing of y-y subunit of IL-2with IL-4, IL-7, IL-9, IL-15 and IL-21, common (3 chains of IL-3, IL-5 and GM-CSF and common a chain for IL-4 and IL-13. gpl30, which is a second chain required for IL-6-a activity, is also a trigger for several other cytokines. The binding of the cytokine to the double chain renders a dual affinity as is the case for IL-2, IL-3, IL-5, IL-7 and GM-CSF. 

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