Mitogens increase phosphorylation of phosphoinositides in thymocytes.
In many cell systems the interaction of ligands with their receptors causes rapid breakdown and resynthesis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Recent work has focused on the role of the degradation products of PtdIns(4,5)P2 as intermediates in the activation of cell function and growth: inositol trisphosphate (InsP3) can release Ca2+ from intracellular stores and diacylglycerol is thought to activate protein kinase C. This enzyme is also activated by phorbol esters (for example, 12-O-tetradecanoyl phorbol 13-acetate, TPA) and this is assumed to account for the pleiotropic effects of TPA on cell function and growth. Mouse thymocytes are not mitogenically stimulated by TPA alone, but it is a potent co-mitogen in combination with either concanavalin A (Con A) or A23187 (A. N. Corps and J.C.M., unpublished observations). Here we show that mitogenic concentrations of TPA, A23187 and Con A each cause an increase in the net phosphorylation of phosphatidylinositol (PtdIns) to PtdIns(4,5)P2 in mouse thymocytes. This is consistent with simulation by the mitogens of the same phosphoinositide phosphorylations in intact cells as recently demonstrated for the isolated products of the src and ros viral oncogenes in a cell-free system.
D000818:Animals; D001386:Azides / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001386:Azides; D010716:Phosphatidylinositols; D003208:Concanavalin A; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate