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International Immunology, Vol. 12, No. 11, 1547-1552, November 2000
© 2000 Japanese Society for Immunology

Role of Tec kinase in nuclear factor of activated T cells signaling

Wen-Chin Yang2, Marguerite Ghiotto, Rémy Castellano, Yves Collette, Nathalie Auphan1, Jacques A. Nunès and Daniel Olive

INSERM U119, Institut d'Immunologie et de Cancérologie de Marseille, Université de la Méditerranée, 27 Bd Leï Roure, 13009 Marseille, France
1 Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, 13288 Marseille, France

Correspondence to: J. A. Nunès or D. Olive

The Tec protein kinase family includes Btk, Itk, Tec, Rlk and Bmx, which are critically involved in signals mediated by various cytokines and antigen receptors. Btk mutations cause severe immunodeficiencies, with defective B cell function. In T cells, Tec regulates cytokine production. However, the downstream targets of these Tec kinases are poorly defined. Here we report that overexpression of Tec in T cells can regulate gene transcription through the nuclear factor of activated T cells (NF-AT). Using different reporter gene constructs, we establish that Tec in transfected T cells dramatically induced NF-AT-dependent gene transcription, which was prevented by a dominant-negative mutant of NF-AT or by the immunosuppressive drug cyclosporin A. Tec appears to regulate NF-AT nuclear import. In addition, Tec influences cytoplasmic free calcium increase. Taken together, our results identify NF-AT as a major downstream target of Tec kinases that is critically involved in transcriptional gene regulation. These observations highlight signaling pathways regulated by Tec kinases and provide new pharmacological targets to regulate immune functions.

Keywords: signal transduction, T cells, Tec family kinases, transcription factors

2 Present address: Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA

Transmitting editor: L. Moretta


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