Tyrosine phosphorylation of the p85 subunit of phosphatidylinositol 3-kinase correlates with high proliferation rates in sublines derived from the Jurkat leukemia

A prominent tyrosine phosphorylated protein of 85 kDa (p85) was detected in highly proliferative sublines derived from the Jurkat T cell leukemia. We undertook a study to characterize the identity of this protein and its poss ible role in the hyperproliferative phenotypes observed. Using immunoblot a nd immunoprecipitation techniques, this protein was characterized as the p8 5 regulatory subunit of phosphatidylinositol 3-kinase. Cell proliferation a nd p85 tyrosine phosphorylation was not affected by tyrphostin AG-490, an i nhibitor of Jak kinases, wortmannin or LY294002, inhibitors of the activity of the catalytic phosphatidylinositol 3-kinase subunit. Herbimycin-A and P PI, inhibitors of ac-like protein tyrosine kinases, and genistein, a genera l tyrosine kinase inhibitor, inhibited p85 tyrosine phosphorylation and ind uced cell death in the sublines, PD98059, an inhibitor of Mek, inhibited ce ll growth of the sublines, but not that of the parental cells. It was concl uded that tyrosine phosphorylation of p85 is associated with highly prolife rative tumoral phenotypes. at least in T cell leukemias, independent of the phosphatidylinositol 3-kinase activity of the catalytic subunit, (C) 2000 Elsevier Science Ltd. All rights reserved.