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The Journal of Immunology, Vol 154, Issue 5 2033-2040, Copyright © 1995 by American Association of Immunologists
ARTICLES |
MA Goldsmith, MC Amaral and WC Greene
Gladstone Institute of Virology and Immunology, San Francisco General Hospital, CA.
The biologic actions of IL-2 are mediated by the IL-2R, a multisubunit receptor complex displayed on the surface of lymphocytes and select other hematopoietic lineages. The IL-2R exhibits multiple affinities for IL-2 that result from the monomeric (alpha), heterodimeric (alpha beta and beta gamma), and heterotrimeric (alpha beta gamma) assembly of different receptor subunits. In the present studies, we have used a series of IL-2R mutants in a transient mammalian expression system to investigate the potential role of intracellular receptor regions in the ligand-binding functions of the IL-2R. Analyses of chimeric and deletion mutants of the IL-2R beta subunit have revealed that its intracellular domain critically and selectively influences high affinity ligand binding mediated through the extracellular domains of the alpha beta-heterodimeric receptor. In contrast, intermediate affinity binding of IL-2 by beta gamma-heterodimeric receptors exhibits no dependence on the cytoplasmic domain of IL-2 R beta. Further, co- expression of either a full-length or severely truncated form of IL-2 R gamma to generate an alpha beta gamma-heterotrimeric complex also overcomes the functional dependence upon the cytoplasmic tail of IL-2 R beta. Collectively, our findings suggest that the cytoplasmic domain of IL-2R beta produces intrasubunit transmembrane conformational changes in this receptor subunit that promote extracellular IL-2 binding in combination with IL-2R alpha. These findings have important implications for the receptor dynamics involved in both ligand binding and signal transduction as well as for clinical applications pertaining to altering IL-2R function.
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K. D. Liu, S. Y. Lai, M. A. Goldsmith, and W. C. Greene Identification of a Variable Region within the Cytoplasmic Tail of the IL-2 Receptor beta Chain That Is Required for Growth Signal Transduction J. Biol. Chem., September 22, 1995; 270(38): 22176 - 22181. [Abstract] [Full Text] [PDF] |
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