RECEPTOR-STIMULATED ACCUMULATION OF PHOSPHATIDYLINOSITOL (3,4,5)-TRISPHOSPHATE BY G-PROTEIN MEDIATED PATHWAYS IN HUMAN MYELOID DERIVED CELLS

Phosphoinositide 30H-kinase (PI3K) activities are thought to be critic al regulatory enzymes in a new intracellular signalling pathway, the a ctivation of which results in the rapid accumulation of a putative sig nalling molecule, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3 ,4,5) P3]. 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 transduc tion pathways can stimulate very rapid and large accumulations of PtdI ns(3,4,5)P3 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 anti-phosp hotyrosine and anti-src-type PTK antibody directed immunoprecipitates, indicating activation of PI3K via a 'conventional' PTK mediated mecha nism; these pathways however, play only a minor role in the initial, a gonist sensitive production of PtdIns(3,4,5)P3 in myeloid derived cell s.