Regulation of phospholipase A2 in human leukemia cell lines: its implication for intracellular signaling.
Permeabilized human leukemia HL-60 and U-937 cells suspended in an acidic or alkaline medium release various unsaturated fatty acids, most abundantly oleic and arachidonic acids. Concomitant production of lysophospholipids suggests that phospholipases A2 play a major role in this fatty acid release reaction. The fatty acid release at acidic conditions depends on the intracellular Ca2+ concentrations at the 10(-8)-10(-7) M range and is enhanced by membrane-permeant diacylglycerols, although this enhancement seems independent of protein kinase C activation. On the other hand, the fatty acid release at alkaline conditions is potentiated by vanadate, and this potentiation is counteracted by genistein, suggesting a role of tyrosine phosphorylation in this release reaction. GTP[gamma S], an activator of G proteins, greatly enhances the fatty acid release. Aluminum fluoride, another activator of heterotrimeric G proteins, also greatly potentiates this release reaction. Phorbol ester increases the fatty acid release at alkaline conditions, to some extent, whereas it counteracts the vanadate-induced potentiation of fatty acid release. The results imply that several phospholipases A2 are coupled to receptors for their activation, thereby functioning in the transmembrane control of cellular events.
Department of Biochemistry, Kobe University School of Medicine, Japan.
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Tsujishita
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Asaoka
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Nishizuka
D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability; D004075:Diglycerides / Q000494:pharmacology; D018274:Electroporation; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D019833:Genistein; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D012969:Sodium Fluoride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology
D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D007529:Isoflavones; D013873:Thionucleotides; C044295:1,2-dioctanoylglycerol; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014638:Vanadates; C023427:guanosine 5'-O-(2-thiodiphosphate); D012969:Sodium Fluoride; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium