A wortmannin-sensitive phosphatidylinositol 4-kinase that regulates hormone-sensitive pools of inositolphospholipids

作者: S. Nakanishi , K. J. Catt , T. Balla

DOI: 10.1073/PNAS.92.12.5317

关键词: KinaseWortmanninJurkat cellsBiochemistryInositolCell biologyIntracellularBiology3T3 cellsPhosphatidylinositolCytoplasm

摘要: The synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], the immediate precursor intracellular signals generated by calcium-mobilizing hormones and growth factors, is initiated conversion to 4-phosphate [PtdIns(4)P] 4-kinase (PtdIns 4-kinase). Although cells contain several PtdIns 4-kinases, enzyme responsible for regulating hormone-sensitive PtdIns(4,5)P2 pools has not been identified. In this report we describe inhibitory effect micromolar concentrations wortmannin (WT) on PtdIns(4)P in intact adrenal glomerulosa cells, presence a WT-sensitive adrenocortical extracts. addition its sensitivity 3-kinase inhibitor WT, distinguished from recognized membrane-bound 4-kinases molecular size weak membrane association. Inhibition WT results rapid loss pool angiotensin II-stimulated cells. Consequently, treatment inhibits sustained but initial increases inositol 1,4,5-trisphosphate cytoplasmic [Ca2+] variety agonist-stimulated including NIH 3T3 fibroblasts, Jurkat lymphoblasts. These indicate that specific critical maintenance agonist-sensitive polyphosphoinositide cell types.

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