Affiliation:
1. Department of Medicine and Howard Hughes Medical Institute, University of California, San Francisco, California 94143
Abstract
ABSTRACT
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 Cγ (PLC-γ) 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-γ, but not the adapters LAT, SLP-76, and BLNK, which are required for Btk and Itk to couple to PLC-γ. 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.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference36 articles.
1. Phosphatidylcholine hydrolysis activates NF-kappa B and increases human immunodeficiency virus replication in human monocytes and T lymphocytes
2. Bunnell, S. C., D. I. Hong, J. R. Kardon, T. Yamazaki, C. J. McGlade, V. A. Barr, and L. E. Samelson. 2002. T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J. Cell Biol. 158 : 1263-1275.
3. Ching, K. A., J. A. Grasis, P. Tailor, Y. Kawakami, T. Kawakami, and C. D. Tsoukas. 2000. TCR/CD3-induced activation and binding of Emt/Itk to linker of activated T cell complexes: requirement for the Src homology 2 domain. J. Immunol. 165 : 256-262.
4. Ching, K. A., Y. Kawakami, T. Kawakami, and C. D. Tsoukas. 1999. Emt/Itk associates with activated TCR complexes: role of the pleckstrin homology domain. J. Immunol. 163 : 6006-6013.
5. Dietrich, J., X. Hou, A. M. Wegener, and C. Geisler. 1994. CD3 gamma contains a phosphoserine-dependent di-leucine motif involved in down-regulation of the T cell receptor. EMBO J. 13 : 2156-2166.
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