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Molecular and Cellular Biology, March 2004, p. 2455-2466, Vol. 24, No. 6
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.6.2455-2466.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Expression and Function of Tec, Itk, and Btk in Lymphocytes: Evidence for a Unique Role for Tec

Michael G. Tomlinson, Lawrence P. Kane,{dagger} Jennifer Su,{ddagger} Theresa A. Kadlecek, Marianne N. Mollenauer, and Arthur Weiss*

Department of Medicine and Howard Hughes Medical Institute, University of California, San Francisco, California 94143

Received 2 September 2003/ Returned for modification 6 October 2003/ Accepted 19 December 2003

The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. Btk is essential for B-cell receptor signaling, because mutations in Btk are responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice, whereas Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, but its role in antigen receptor signaling is not clear. In this study, we show that Tec protein is expressed at substantially lower levels in primary T and B cells relative to Itk and Btk, respectively. However, Tec is up-regulated upon T-cell activation and in Th1 and Th2 cells. In functional experiments that mimic Tec up-regulation, we find that Tec overexpression in lymphocyte cell lines is sufficient to induce phospholipase C{gamma} (PLC-{gamma}) phosphorylation and NFAT (nuclear factor of activated T cells) activation. In contrast, overexpression of Btk, Itk, or Bmx does not induce NFAT activation. Tec-induced NFAT activation requires PLC-{gamma}, but not the adapters LAT, SLP-76, and BLNK, which are required for Btk and Itk to couple to PLC-{gamma}. Finally, we show that the unique effector function for Tec correlates with a unique subcellular localization. We hypothesize that Tec functions in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors.

* Corresponding author. Mailing address: Department of Medicine and Howard Hughes Medical Institute, University of California at San Francisco, 533 Parnassus St., San Francisco, CA 94143. Phone: (415) 476-1291. Fax: (415) 502-5081. E-mail: aweiss{at}medicine.ucsf.edu.

{dagger} Present address: Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261.

{ddagger} Present address: School of Medicine, Johns Hopkins University, Baltimore, MD 21205.

Molecular and Cellular Biology, March 2004, p. 2455-2466, Vol. 24, No. 6
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.6.2455-2466.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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