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PNAS 97 (21): 11439-11444

Copyright © 2000 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / IMMUNOLOGY

Cloning of a type I cytokine receptor most related to the IL-2 receptor β chain

Katsutoshi Ozaki*, Kristine Kikly{dagger}, David Michalovich{ddagger}, Peter R. Young§,¶, and Warren J. Leonard*,||

*Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674; and Departments of {dagger}Immunology, {ddagger}Bioinformatics, and §Molecular Biology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406-0939

Accepted for publication August 1, 2000.

Received for publication May 19, 2000.

Abstract: We have identified a type I cytokine receptor, which we have termed novel interleukin receptor (NILR), that is most related to the IL-2 receptor β chain (IL-2Rβ) and physically adjacent to the IL-4 receptor α chain gene on chromosome 16. NILR mRNA is most highly expressed in thymus and spleen, and is induced by phytohemagglutinin in human peripheral blood mononuclear cells. NILR protein was detected on human T cell lymphotropic virus type I-transformed T cell lines, Raji B cells, and YT natural killer-like cells. Artificial homodimerization of the NILR cytoplasmic domain confers proliferation to Ba/F3 murine pro-B cells but not to 32D myeloid progenitor cells or CTLL-2 murine helper T cells. In these latter cells, heterodimerization of IL-2Rβ and the common cytokine receptor {gamma} chain ({gamma}c) cytoplasmic domains allows potent proliferation, whereas such heterodimerization of NILR with {gamma}c does not. This finding suggests that NILR has signaling potential but that a full understanding of its signaling partner(s) is not yet clear. Like IL-2Rβ, NILR associates with Jak1 and mediates Stat5 activation.

Present address: Cardiovascular Diseases, DuPont Pharmaceuticals, Experimental Station, E400/3257, Route 141, Henry Clay Road, Wilmington, DE 19880-0400.

|| To whom reprints requests should be addressed. E-mail: wjl{at}helix.nih.gov.

Communicated by William E. Paul, National Institutes of Health, Bethesda, MD

Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF269133 and AF269134).

Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.200360997.

Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.200360997

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