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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 Rajagopala, Connie L. Sommersb, Donna C. Deckerc, Elizabeth O. Mitchellc, Ulf Korthauerc, Anne I. Sperlinga,d, Christine A. Kozake, Paul E. Loveb, and Jeffrey A. Bluestonea,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
Ben May Institute for Cancer Research, University of Chicago, MC 1089, 5482 South Maryland Ave., Chicago, IL 60637.773-702-3701773-702-0401

jbluest{at}immunology.uchicago.edu

A novel T cell–specific adaptor protein, RIBP, was identified based on its ability to bind Rlk/Txk in a yeast two-hybrid screen of a mouse T cell lymphoma library. RIBP was also found to interact with a related member of the Tec family of tyrosine kinases, Itk. Expression of RIBP is restricted to T and natural killer cells and is upregulated substantially after T cell activation. RIBP-disrupted knockout mice displayed apparently normal T cell development. However, proliferation of RIBP-deficient T cells in response to T cell receptor (TCR)-mediated activation was significantly impaired. Furthermore, these activated T cells were defective in the production of interleukin (IL)-2 and interferon {gamma}, but not IL-4. These data suggest that RIBP plays an important role in TCR-mediated signal transduction pathways and that its binding to Itk and Rlk/Txk may regulate T cell differentiation.

Key Words: T cell activation • signal transduction • adaptor protein • Tec tyrosine kinases • T helper type 1/T helper type 2 cells

Abbreviations used in this paper: ES, embryonic stem; KO, knockout; PRR, proline-rich region; PTB, phosphotyrosine-binding; PTK, protein tyrosine kinase; RAG, recombinase-activating gene; RIBP, Rlk/Itk-binding protein; SH, Src homology; TBST, Tris-buffered saline/Tween.

© 1999 The Rockefeller University Press


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