Interleukin-2 and the IL-2 receptor: new insights into structure and function.
Interleukin-2 (IL-2) was originally identified in 1976 as a growth factor for T lymphocytes. Since that time it has become an important mediator of immune function through its effects on the growth, development, and activity of T and B lymphocytes, natural killer cells, and lymphokine-activated killer cells. Only cells that bear a specific receptor for IL-2 respond to its immunoregulatory effects. Of all the lymphokine-receptor systems in immunology, perhaps most is known about the structure, function, and binding properties of IL-2 and its cognate receptor. There are two distinct, membrane-associated IL-2 binding components in the high-affinity IL-2 receptor: an alpha subunit and a beta subunit, which associate in a non-covalent manner. Each of these polypeptides can occur on the cell surface in the absence of the other and bind IL-2, although with only low or intermediate affinity relative to the high-affinity receptor complex. The primary structure of each chain has now been deduced from full-length cDNA. The rapid rate of association between IL-2 and the IL-2R alpha subunit is important in the formation of high-affinity binding sites, and the inducibility of the alpha gene contributes to the highly regulated and transient display of high-affinity IL-2R. The IL-2R beta chain controls the slow dissociation rate of IL-2 from the high-affinity receptor. Also, IL-2R beta appears centrally involved in internalization of IL-2 and signal transduction, functions mediated presumably through its long intracytoplasmic domain. However, the actual mechanism of signal transduction in the IL-2/IL-2R system remains undefined. IL-2R beta is a member of a novel family of cytokine-receptor proteins that includes receptors for IL-4, IL-6, and erythropoietin.
Kuziel
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Howard Hughes Medical Institute, Department of Medicine, Durham, North Carolina.
Greene
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D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000235:genetics; D004355:Drug Stability; D000939:Epitopes; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D008969:Molecular Sequence Data; D015375:Receptors, Interleukin-2 / Q000145:classification / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D000939:Epitopes; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D004247:DNA