Structure and function of IL-2 and IL-2 receptors.
Cytokines, a class of soluble mediators involved in cell-to-cell communication, are generated in response to many stimuli by a variety of tissues. They include interferons (IFNs), Interleukins (ILs) and colony stimulation factors (CSFs), and have been most extensively studied in the context of hematopoiesis and immune responses, however their molecular nature remained totally elusive due to the scarcity of the cytokines produced, under optimized conditions for producer cells. With the advent of recombinant DNA technology, we have isolated in 1983 the gene encoding one of the first identified Interleukins, IL-2, and thus initiated our molecular analyses of the IL-2 system. In fact, IL-2 plays a major role in the clonal expansion of T lymphocytes (T cells) by interacting with specific cell surface receptor (IL-2 receptor). The functional, high-affinity form of IL-2 receptor (IL-2R) is composed of two receptor components, IL-2R alpha (p55) and IL-2R beta (p70-75) chains. We have cloned a human and murine IL-2R beta cDNAs. Unlike the IL-2R alpha chain, the IL-2R beta chain contains a large cytoplasmic domain which shows no obvious tyrosine kinase motif. We established a system in which the cDNA-directed human IL-2R beta allows growth signal transduction in murine IL-3-dependent cell lines. Utilizing this system, we have identified a cytoplasmic region of the receptor critical for the growth signal transduction. Furthermore, we have provided evidence for the physical association of IL-2R beta with protein tyrosine kinase, 56lck. The functional significance of such association may be profound in understanding the general mechanisms of cytokine-induced signal transduction.
Taniguchi
T
T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003001:Cloning, Molecular; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2