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.

Download full-text


Available from: Pamela L Schwartzberg
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although the T-cell-mediated immune response to influenza virus has been studied extensively, little information is available on the direct interaction between influenza virus and T-cells that pertains to severe diseases in humans and animals. To address these issues, we utilized the BALB/c mouse model combined with primary T-cells infected with A/WSN/33 influenza virus to investigate whether influenza virus has an affinity for T-cells in vivo. We observed that small proportions of CD4(+) T-cells and CD8(+) T-cells in spleen and thymus expressed viral proteins in infected mice. A significant proportion of mouse primary T-cells displayed expression of α-2,6 sialic acid-linked influenza virus receptor and were infected directly by influenza A virus. These experiments reveal that there exists a population of T-cells that is susceptible to influenza A virus infection. Furthermore, we employed human Jurkat T-cells to investigate the virus-T-cell interaction, with particular emphasis on understanding whether Itk (interleukin-2-inducible T-cell kinase), a Tec family tyrosine kinase that regulates T-cell activation, is involved in virus infection of T-cells. Interestingly, influenza virus infection resulted in an increased recruitment of Itk to the plasma membrane and an increased level of phospholipase C-γ1 (PLC-γ1) phosphorylation, suggesting that Itk/PLC-γ1 signalling is activated by the virus infection. We demonstrated that depletion of Itk inhibited the replication of influenza A virus, whereas overexpression of Itk increased virus replication. These results indicate that Itk is required for efficient replication of influenza virus in infected T-cells.
    Preview · Article · Feb 2012 · Journal of General Virology
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The adapter molecule LAT is a nucleating site for multiprotein signaling complexes that are vital for the function and differentiation of T cells. Extensive investigation of LAT in multiple experimental systems has led to an integrated understanding of the formation, composition, regulation, dynamic movement, and function of LAT-nucleated signaling complexes. This review discusses interactions of signaling molecules that bind directly or indirectly to LAT and the role of cooperativity in stabilizing LAT-nucleated signaling complexes. In addition, it focuses on how imaging studies visualize signaling assemblies as signaling clusters and demonstrate their dynamic nature and cellular fate. Finally, this review explores the function of LAT based on the interpretation of mouse models using various LAT mutants.
    Full-text · Article · Aug 2010 · Cold Spring Harbor perspectives in biology
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The Tec family tyrosine kinases regulate lymphocyte development, activation, and differentiation. In T cells, the predominant Tec kinase is Itk, which functions downstream of the T-cell receptor to regulate phospholipase C-gamma. This review highlights recent advances in our understanding of Itk kinase structure and enzymatic regulation, focusing on Itk protein domain interactions and mechanisms of substrate recognition. We also discuss the role of Itk in the development of conventional versus innate T-cell lineages, including both alphabeta and gammadelta T-cell subsets. Finally, we describe the complex role of Itk signaling in effector T-cell differentiation and the regulation of cytokine gene expression. Together, these data implicate Itk as an important modulator of T-cell signaling and function.
    Full-text · Article · Jul 2010 · Cold Spring Harbor perspectives in biology
Show more