Abstract
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)1–5. 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 growth6: inositol trisphosphate (InsP3) can release Ca2+ from intracellular stores7–9 and diacylglycerol is thought to activate protein kinase C6,10. This enzyme is also activated by phorbol esters (for example, 12-O-tetradecanoy1 phorbol 13-acetate, TPA)11 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but it is a potent co-mitogen in combination with either concanavalin A (Con A) or A23187 (A. N. Corps and J.C.M., unpublished observations).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 A12 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 system13,14.
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Taylor, M., Metcalfe, J., Hesketh, T. et al. Mitogens increase phosphorylation of phosphoinositides in thymocytes. Nature 312, 462–465 (1984). https://doi.org/10.1038/312462a0
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DOI: https://doi.org/10.1038/312462a0
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