Tek family kinases, such as Btk and Itk, are non-receptor tyrosine kinases related to the Src family. Initially shown to be important in immune cells for Ca2+ mobilization during antigen receptor signalling, Tek kinases function downstream of cell-surface receptors from Fc receptors to integrins. In a Commentary on p. 3039, Pamela Schwartzberg and co-workers review our understanding of the roles of these kinases in signalling. Tek kinases possess the SH1, SH2 and SH3 domains characteristic of Src kinases but contain additional, pleckstrin-homology (PH) and proline-rich (PR) domains. The PH domain regulates membrane targeting by binding to phospholipids such as the PI 3-kinase product PtdIns(3,4,5)P3. The PR domain appears to engage in inter- and intra-molecular PR-SH3 interactions, disruption of which could activate the kinase. Once activated, Tek kinases regulate Ca2+ signalling by phosphorylating phospholipase Cγ. However, they also regulate signalling by MAP kinases and STATs, as well as by actin reorganization. Indeed interactions between Tek kinases and actin regulators such as WASP could be critical for formation of the immunological synapse required for sustained signalling by T-cell receptors.
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