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 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) 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 transduction pathways can stimulate very rapid and large accumulations of PtdIns(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-phosphotyrosine 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)P3 in myeloid derived cells.
Biochemistry Department, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, UK.
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Stephens
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Eguinoa
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Corey
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Jackson
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Hawkins
D000255:Adenosine Triphosphate / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction
D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C060974:phosphatidylinositol 3,4,5-triphosphate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins