RIBP, a Novel Rlk/Txk- and Itk-binding Adaptor Protein That Regulates T Cell Activation

doi:10.1084/jem.190.11.1657

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© The Rockefeller University Press, 0022-1007/1999/12/1657/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 11, December 6, 1999 1657-1668

Original Article

RIBP, a Novel Rlk/Txk- and Itk-binding Adaptor Protein That Regulates T Cell Activation

Keshava Rajagopal^a, Connie L. Sommers^b, Donna C. Decker^c, Elizabeth O. Mitchell^c, Ulf Korthauer^c, Anne I. Sperling^a,d, Christine A. Kozak^e, Paul E. Love^b, and Jeffrey A. Bluestone^a,c
^a Committee on Immunology, University of Chicago, Chicago, Illinois 60637
^b Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892
^c Ben May Institute for Cancer Research, Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois 60637
^d Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois 60637
^e Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Correspondence to: Jeffrey A. Bluestone, Ben May Institute for Cancer Research, University of Chicago, MC 1089, 5482 South Maryland Ave., Chicago, IL 60637. Tel:773-702-0401 Fax:773-702-3701 E-mail:jbluest{at}immunology.uchicago.edu.

A novel T cell–specific adaptor protein, RIBP, was identifiedbased on its ability to bind Rlk/Txk in a yeast two-hybrid screenof a mouse T cell lymphoma library. RIBP was also found to interactwith a related member of the Tec family of tyrosine kinases,Itk. Expression of RIBP is restricted to T and natural killercells and is upregulated substantially after T cell activation.RIBP-disrupted knockout mice displayed apparently normal T celldevelopment. However, proliferation of RIBP-deficient T cellsin response to T cell receptor (TCR)-mediated activation wassignificantly impaired. Furthermore, these activated T cellswere defective in the production of interleukin (IL)-2 and interferon ${gamma}$ , but not IL-4. These data suggest that RIBP plays an importantrole in TCR-mediated signal transduction pathways and that itsbinding to Itk and Rlk/Txk may regulate T cell differentiation.

Key Words: T cell activation, signal transduction, adaptor protein, Tectyrosine kinases, T helper type 1/T helper type 2 cells

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