REGULATION OF PHOSPHOLIPASE A(2) IN HUMAN LEUKEMIA-CELL LINES - ITS IMPLICATION FOR INTRACELLULAR SIGNALING

Permeabilized human leukemia HL-60 and U-937 cells suspended in an aci dic or alkaline medium release various unsaturated fatty acids, most a bundantly oleic and arachidonic acids. Concomitant production of lysop hospholipids suggests that phospholipases A(2) play a major role in th is fatty acid release reaction. The fatty acid release at acidic condi tions 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 activa tion. 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 relea se reaction. GTP[gamma S], an activator of G proteins, greatly enhance s the Patty acid release. Aluminum fluoride, another activator of hete rotrimeric 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 potentia tion of fatty acid release. The results imply that several phospholipa ses A(2) are coupled to receptors for their activation, thereby functi oning in the transmembrane control of cellular events.