Activation of phosphatidylinositol‐3‐kinase in Jurkat T cells depends on the presence of the p56lcktyrosine kinase

摘要

AbstractActivation of resting T lymphocytes by ligands to the T cell receptor (TcR)/CD3 complex is initiated by phosphorylation of a number of key regulatory proteins on specific tyrosine residues. One such protein is the heterodimeric enzyme phosphatidylinositol‐3‐kinase (PI3K). We recently found that this enzyme is also rapidly activated following TcR/CD3 triggering and that immunoprecipitated PI3K was activatedin vitroby direct tyrosine phosphorylation. Here we show that TcR/CD3‐induced tyrosine phosphorylation and activation of PI3K in Jurkat T leukemia cells depend on the presence of the p56lcktyrosine kinase: in a variant of the Jurkat T cell line lacking p56lck, JCaM1, these responses were absent. We also show that p56lckdirectly activates PI3K purified from transfected COS‐1 cells, indicating that other T cell‐specific proteins are not required for the process. Finally, tryptic peptide maps show that p56lckphosphorylates three tyrosine residues in the p85α subunit of PI3K and two in p110 of PI3K. Our results suggest that p56lckis required for activation of PI3K in Jurkat T cells and can itself directly activate it by phosphorylating one or several stimula