Interaction of SLP adaptors with the SH2 domain of Tec family kinases

Activation of lymphocytes through their antigen receptors leads to mobiliza tion of intracellular Ca2+ ions. This process requires expression of SLP ad aptors and involves phosphorylation of phospholipase C-gamma isoforms by th e Tec-related protein tyrosine kinase Btk in B cells and Itk in T cells. Th e SH2 domain of Btk and Itk is essential for phospholipase C-gamma phosphor ylation and mutations in this domain lead to the X-linked agammaglobulinemi a immunodeficiency in humans. Here we show that, in contrast to SH2 domains from other signaling proteins, the Btk and Itk SH2 domains exhibit a restr icted binding specificity. They bind selectively to tyrosine-phosphorylated SLP-65 and SLP-76 in activated B and T cells, respectively. Our findings s uggest that Btk/Itk and phospholipase C-gamma both bind via their SH2 domai n to phosphorylated SLP adaptors, and that this association is required for the activation of phospholipase C-gamma.