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.
Tsujishita
Y
Y
Department of Biochemistry, Kobe University School of Medicine, Japan.
Asaoka
Y
Y
Nishizuka
Y
Y
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