Tec kinase signaling in T cells is regulated by phosphatidylinositol 3-kinase and the Tec pleckstrin homology domain
Department of Pathology
1-Phosphatidylinositol 3-Kinase; Amino Acid Substitution; Androstadienes; Animals; Arginine; Blood Proteins; Cysteine; Enzyme Inhibitors; Glutamic Acid; Humans; Interleukin-2; Jurkat Cells; Lysine; Mice; Mice, Transgenic; Phosphatidylinositol Phosphates; Phosphoproteins; Phosphorylation; Phosphotyrosine; Protein Binding; Protein Structure, Tertiary; Protein-Tyrosine Kinases; Receptor-CD3 Complex, Antigen, T-Cell; Receptors, Antigen, T-Cell; *Sequence Homology, Amino Acid; Signal Transduction; T-Lymphocytes; Transfection
Life Sciences | Medicine and Health Sciences
Tec, the prototypical member of the Tec family of tyrosine kinases, is abundantly expressed in T cells and other hemopoietic cell types. Although the functions of Itk and Txk have recently been investigated, little is known about 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 pleckstrin homology (PH) domain. Using several PH domain mutants overexpressed in Jurkat T cells, we show that the Tec PH domain is required for Tec-mediated IL-2 gene induction and TCR-mediated Tec tyrosine phosphorylation. Furthermore, 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 association. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, abolishes Tec-mediated IL-2 gene induction and Tec tyrosine phosphorylation, and partially suppresses Tec colocalization with the activated TCR. Thus, our data implicate the Tec kinase PH domain and phosphatidylinositol 3-kinase in Tec signaling downstream of the TCR.
DOI of Published Version
J Immunol. 2001 Jan 1;166(1):387-95.
Journal of immunology (Baltimore, Md. : 1950)
Yang, Wen-Chin; Ching, Keith A.; Tsoukas, Constantine D.; and Berg, Leslie J., "Tec kinase signaling in T cells is regulated by phosphatidylinositol 3-kinase and the Tec pleckstrin homology domain" (2000). Open Access Articles. 1130.