Cloning of the Murine Thymic Stromal Lymphopoietin (TSLP) Receptor: Formation of a Functional Heteromeric Complex Requires Interleukin 7 Receptor

doi:10.1084/jem.192.5.659

Published online 28 August 2000.

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© The Rockefeller University Press, 0022-1007/2000/9/659/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 5, September 5, 2000 659-670

Original Article

Cloning of the Murine Thymic Stromal Lymphopoietin (TSLP) Receptor: Formation of a Functional Heteromeric Complex Requires Interleukin 7 Receptor

Linda S. Park^a, Unja Martin^a, Kirsten Garka^a, Brian Gliniak^a, James P. Di Santo^b, Werner Muller^c, David A. Largaespada^d, Neal G. Copeland^d, Nancy A. Jenkins^d, Andrew G. Farr^e, Steven F. Ziegler^f, Philip J. Morrissey^a, Raymond Paxton^a, and John E. Sims^a
^a Department of Biochemistry, Department of Biological Sciences, and the Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101
^b Departement d'Immunologie, Institut Pasteur, 75724 Paris, France
^c Institute for Genetics, Cologne D-50931, Germany
^d Mammalian Genetics Laboratory, ABL-Basic Research Program National Cancer Institute–Frederick Cancer Research and Development Center, Frederick, Maryland 21702
^e Department of Biological Structure, University of Washington, Seattle, Washington 98195
^f Virginia Mason Research Center, Seattle, Washington 98101

Correspondence to: John E. Sims, Immunex Corporation, 51 University St., Seattle, WA 98101. Tel:206-587-0430 Fax:206-233-9733 E-mail:sims{at}immunex.com.

The cellular receptor for murine thymic stromal lymphopoietin(TSLP) was detected in a variety of murine, but not human myelomonocyticcell lines by radioligand binding. cDNA clones encoding thereceptor were isolated from a murine T helper cell cDNA library.TSLP receptor (TSLPR) is a member of the hematopoietin receptorfamily. Transfection of TSLPR cDNA resulted in only low affinitybinding. Cotransfection of the interleukin 7 (IL-7)R ${alpha}$ chain cDNAresulted in conversion to high affinity binding. TSLP did notactivate cells from IL-7R ${alpha}$ ^-/- mice, but did activate cells from ${gamma}$ c^-/- mice. Thus, the functional TSLPR requires the IL-7R ${alpha}$ chain,but not the ${gamma}$ c chain for signaling.

Key Words: cytokine receptors, interleukin 2 receptor, interleukin 7 receptor,cytokine, DNA sequence

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