RESUMO
Itk/Emt, a tec family tyrosine kinase, is important for T-cell development and activation through the antigen receptor. Here, we review data suggesting that Itk/Emt is involved in the generation of critical second messengers (Ca(2+), PKC) whose duration it modulates by regulation of cytoskeletal reorganization. We propose that Itk/Emt constitutes an important link between these critical signaling events.
Assuntos
Sinalização do Cálcio , Citoesqueleto/enzimologia , Citoesqueleto/imunologia , Proteínas Tirosina Quinases/metabolismo , Receptores de Antígenos de Linfócitos T/fisiologia , Animais , Ativação Enzimática/imunologia , Humanos , Linfócitos T/enzimologia , Linfócitos T/metabolismoRESUMO
Expressed in mast and T cells/inducible T cell tyrosine kinase (Emt/Itk), a Tec family protein tyrosine kinase, is critical for the development and activation of T lymphocytes. The mechanism through which Emt/Itk mediates its effector functions is poorly understood. In this study, we show that the Emt/Itk Src homology 2 (SH2) domain is critical for the transphosphorylation and activation of Emt/Itk catalytic activity that is mediated by TCR/CD3 engagement. Furthermore, we find that the Emt/Itk SH2 domain is essential for the formation of TCR/CD3-inducible Emt/Itk-LAT complexes, whereas the SH3 domain and catalytic activity are not required. The Emt/Itk-linker of activated T cells (LAT) complexes are biologically important because Jurkat T cells with deficient LAT expression (JCaM2) fail to increase Emt/Itk tyrosine phosphorylation upon TCR/CD3 stimulation. Confocal microscopy reveals that in activated cells, LAT complexes colocalize with TCR/CD3. The present data suggest that upon TCR/CD3 engagement, the Emt/Itk SH2 domain mediates the formation of a molecular complex containing Emt/Itk, LAT, and TCR/CD3; this complex is essential for Emt/Itk activation and function.