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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Expression and function of Tec, Itk, and Btk in lymphocytes: evidence for a unique role for Tec.

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 Cgamma ( 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.[1]


  1. Expression and function of Tec, Itk, and Btk in lymphocytes: evidence for a unique role for Tec. Tomlinson, M.G., Kane, L.P., Su, J., Kadlecek, T.A., Mollenauer, M.N., Weiss, A. Mol. Cell. Biol. (2004) [Pubmed]
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