Receptor stimulated accumulation of phosphatidylinositol (3,4,5)-trisphosphate by G-protein mediated pathways in human myeloid derived cells.

Abstract

Phosphoinositide 30H-kinase (PI3K) activities are thought to be critical regulatory enzymes in a new intracellular signalling pathway, the activation of which results in the rapid accumulation of a putative signalling molecule, phosphatidylinositol (3, 4, 5)-trisphosphate [PtdIns(3, 4, 5) P 3 ]. To date, activation of PI3K has always correlated with its recruitment into complexes containing protein tyrosine kinases (PTK). Here we report that agonists which utilize G-protein mediated transduction pathways can stimulate very rapid and large accumulations of PtdIns(3, 4, 5)P 3 via a novel mechanism, possibly involving direct coupling between the G-protein and a PI3K activity. In addition, some of these agonists also stimulate small increases in PI3K activity in antiphosphotyrosine and anti-src-type PTK antibody directed immunoprecipitates, indicating activation of PI3K via a 'conventional' PTK mediated mechanism; these pathways however, play only a minor role in the initial, agonist sensitive production of PtdIns(3, 4, 5)P 3 in myeloid derived cells.