Tec kinase signaling in T cells is regulated by phosphatidylinositol 3-kinase and the Tec pleckstrin homology domain

Tec, the prototypical member of the Tec family of tyrosine kinases, is abun dantly expressed in T cells and other hemopoietic cell types. Although the functions of Itk and Txk have recently been investigated, little is known a bout the role of Tec in T cells, Using antisense oligonucleotide treatment to deplete Tec protein from primary T cells, we demonstrate that Tec plays a role in TCR signaling leading to IL-2 gene induction. Interestingly, Tec kinases are the only known family of tyrosine kinases containing a pleckstr in homology (PH) domain. Using several PH domain mutants overexpressed in J urkat T cells, we show that the Tec PH domain is required for Tee-mediated IL-2 gene induction and TCR-mediated Tec tyrosine phosphorylation, Furtherm ore, we show that Tec colocalizes with the TCR after TCR cross-linking, and that both the Tec PH and Src homology (SH) 2 domains play a role in this a ssociation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, abolishe s Tee-mediated IL-2 gene induction and Tec tyrosine phosphorylation, and pa rtially suppresses Tec colocalization with the activated TCR, Thus, our dat a implicate the Tec kinase PH domain and phosphatidylinositol 3-kinase in T ec signaling downstream of the TCR.