Tec kinases regulate T-lymphocyte development and function: New insights into the roles of Itk and Rlk/Txk

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Immunological Reviews (Impact Factor: 10.12). 04/2009; 228(1):93-114. DOI: 10.1111/j.1600-065X.2008.00757.x
Source: PubMed


The Tec (tyrosine kinase expressed in hepatocellular carcinoma) family of non-receptor tyrosine kinases consists of five members: Tec, Bruton's tyrosine kinase (Btk), inducible T-cell kinase (Itk), resting lymphocyte kinase (Rlk/Txk), and bone marrow-expressed kinase (Bmx/Etk). Although their functions are probably best understood in antigen receptor signaling, where they participate in the phosphorylation and regulation of phospholipase C-gamma (PLC-gamma), it is now appreciated that these kinases contribute to signaling from many receptors and that they participate in multiple downstream pathways, including regulation of the actin cytoskeleton. In T cells, three Tec kinases are expressed, Itk, Rlk/Txk, and Tec. Itk is expressed at highest amounts and plays the major role in regulating signaling from the T-cell receptor. Recent studies provide evidence that these kinases contribute to multiple aspects of T-cell biology and have unique roles in T-cell development that have revealed new insight into the regulation of conventional and innate T-cell development. We review new findings on the Tec kinases with a focus on their roles in T-cell development and mature T-cell differentiation.

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    • "Signalling through the TCR regulates key events in the life of T-cells. The Tec family, an intracytoplasmic tyrosine kinase family, has been recognized as the important mediator of the antigen receptor signalling in lymphocytes and myeloid cells (Andreotti et al., 2010; Felices et al., 2007; Readinger et al., 2009). Itk (interleukin-2-inducible T-cell kinase) is an important member of the Tec family expressed in Tlymphocytes , NK cells and mast cells (Smith et al., 2001). "
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    • "In Vav-deficient T cells, the interaction between SLP-76 and PLC-g1 was substantially reduced and Itk was not phosphorylated (Reynolds et al. 2002; Braiman et al. 2006). The Tec family kinase Itk phosphorylates PLC-g1 (Readinger et al. 2009) and LAT (Perez-Villar et al. 2002). Itk is recruited to the LAT complex by binding of its SH2 domain to tyrosine phosphorylated SLP-76 (Bunnell et al. 2000). "
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    • "A.H. Andreotti et al. and Suzuki 2007; Gilfillan and Rivera 2009; Koprulu and Ellmeier 2009; Prince et al. 2009; Readinger et al. 2009). For Itk, significant attention has been given to activation via T-cell receptor (TCR) stimulation (see Fig. 1B). "
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