The common cytokine receptor gamma chain (γc) family, which consists of interleukin 2 (IL-2), IL-4, IL-7, IL-9, IL-15 and IL-21, and is so named because the receptors for these cytokines share gamma-chain (also known as IL-2Rγ and CD132).
The common gamma-chain (γc) is critical for ligand binding and signaling by common gamma-chain (γc) cytokines. All γc family cytokines similarly activates the Janus kinase (JAK)-family protein tyrosine kinases JAK1 and JAK3, with JAK1 binding a unique α or β chain and JAK3 binding the common gamma-chain (γc). They exert its effect through interaction with gamma-chain (γc) cytokine receptor complex, which is composed of a unique receptor chain and the common gamma-chain (γc).
Below will briefly discuss each common gamma-chain (γc) receptor family member and their functions, including common gamma-chain receptor, IL-4R, IL-7R, IL-9R, IL-15R and IL-21R.
The common gamma-chain (γc) was first discovered as a component of the receptor for IL-2, the prototypic member of this family. The IL-2 receptor (IL-2R) consists of three chains, which together form the high-affinity IL-2R complex, but which in other combinations bind IL-2 with low affinity (IL-2Rα alone) or intermediate affinity (IL-2Rβ and γc).
The common gamma-chain receptor is the only cytokine receptor that is encoded in the X chromosome. Because gamma-chain receptor is subject to X chromosome inactivation, gamma-chain receptor shows monoallelic expression and provides the genetic explanation for X-linked severe combined immunodeficiency (X-SCID).
However, the immune defects in patients with X-SCID are much more severe than those of humans or mice lacking IL-2, in which the development of T and NK cells is intact, originally led to the hypothesis and subsequent confirmation that γc was shared by multiple cytokines.
Combined with the common gamma-chain (γc), IL-4 receptor (IL-4R) becomes an IL-4 receptor complex. The effects of interleukin 4 (IL-4) depend upon binding to and signaling through this receptor complex, resulting in a series of phosphorylation events mediated by receptor-associated kinases. IL-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses.
The IL-7 receptor complex consists of two subunits, IL-7 receptor (IL-7R) and common gamma-chain (γc). IL-7R signaling through is essential for T-cell development and regulation of naive and memory T-cell homeostasis. Some publications demonstrated that soluble IL-7R is closely related with rheumatoid arthritis and multiple sclerosis autoimmune disease.
The IL-9 receptor complex is composed of ligand specific IL-9 receptor (IL-9R) and common gamma-chain (γc). The functions of IL-9 are mediated by the IL-9 receptor complex. IL-9 plays a role in asthma and allergy.
The IL-15 receptor complex consists of IL-15 receptor (IL-15R), IL-2R beta chain and common gamma-chain (γc). Signaling through the IL-15/IL-15R system is of profound clinical importance has become amply clear in rheumatoid arthritis (RA), where IL-15 antibodies have already been tested in Phase I/II trials.
Like other common gamma-chain receptor family members, the IL-21 receptor complex also contains IL-21 receptor (IL-21R) and common gamma-chain (γc). IL-21R, has been shown to activate the Janus kinase/signal transducers and activators of transcription signaling pathway upon ligand binding.
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