I Cytokine Receptor Family

Studies have actually revealed two type I interferon receptor polypeptides. Sequence data from cloning studies place both in the class II cytokine receptor family. Both are transmembrane N-linked glycoproteins. Studies using isolated forms of each show that one polypeptide (called the a/p receptor) is capable of binding all type I interferons. The other one (the ap receptor) is specific for IFN-a-B (a specific member of the IFN-a family). Both receptors are present on most cell types. 

Dr. Alain Fisher and his research team have successfully treated two infants with XSCIDS, a severe form of SCIDS that occurs only in boys. These patients lack functional T cells and natural killer cells (NK) due to mutations in the % chain of the cytokine receptor family that recognizes interleukins (i.e., IL-2, -4, -7, -9, and -15). Ex vivo gene transfer was employed. The researchers delivered the wild-type sequence for the yc chain cytokine receptor subunit to hematopoietic stem cells isolated from these patients using a nonreplicating murine retrovirus [14,15]. 

Fig. 3.1 Families of cytokine receptors the cytokine receptors are classified into five major families immunoglobulin superfamily receptors, type I cytokine receptors, type II cytokine receptors, TNF-like receptors and chemokine receptors. The drawings illustrate their general biochemical structure (see Color Insert)...

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. ... 

The first specifically binds IFNaB (IFNaS, a variety of IFNa) and is known as the IFNaB receptor. The second bmds both IFNa and IFNp and is called the IFNa/j3 receptor. The IFNapR is a member of the class II cytokine receptor family, which also includes the IFNyR, IL-IOR, and tissue factor. The IFNa/ R is also a class II cytokine receptor and contains at least two components that interact with type I IFNs, It is not known if these two receptors are expressed independently on the cell surface or are associated with each other in an IFN receptor complex. The receptors are present on most types of cells. A soluble form of the IFNa/pR has been identified in human serum and urine. 

Elson, G. C., Graber, P., Losberger, C., Herren, S., Gretener, D., Menoud, L. N., Wells, T. N., Kosco-Vilbois, M. H., and Gauchat, J. F. (1998). Cytokine-like factor-1, a novel soluble protein, shares homology with members of the cytokine type I receptor family. / Immunol. 161, 1371-1379. 

The neurotrophin family includes NGF, BDNF, neurotrophin-3 (NT-3), NT-4/5, and NT-6. All neurotrophins are capable of binding to the p75 receptor each neurotrophin also binds to a specific Trk receptor. Trk is the receptor for NGF TrkB is the receptor for BDNF and NT-4, while TrkC is the receptor for NT-3. Neurotrophins secreted by cells protect neurons from apoptosis (Korsching, 1993 Lewin and Barde, 1996). Similarly, ciliary neurotrophic factor (CNTF), a structurally related type I cytokine and GDNF, structurally related to TGF-[3, each constitute a sub-family of neurotrophic factors. 

Many cytokines exhibit redundancy, i.e. two or more cytokines can induce a similar biological effect. Examples include TNF-a and -P, both of which bind to the same receptor and induce very similar, if not identical, biological responses. This is also true of the IFN-a family proteins and IFN-P, all of which bind the same receptor. 

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