H. Inoue et al., POTENTIAL ROLE OF PROTEIN-PHOSPHORYLATION IN GTP-GAMMA-S-DEPENDENT ACTIVATION OF PHOSPHOLIPASE-D, Biochemical and biophysical research communications, 210(2), 1995, pp. 542-548
Mammalian phospholipase D (PLD) is known to require nearly absolutely
guanosine 5'-Q-3-thiotriphosphate (GTP-gamma-S) and a small G-protein
for its activation. In streptolysin-Q-permeabilized HL-60 cells, phorb
ol ester or diacylglycerol enhanced greatly this PLD activation in the
presence of ATP-Mg2+ Nonhydrolysable ATP analogue was inactive. This
phorbol-ester-induced PLD activation was completely counteracted not o
nly by protein kinase C (PKC) inhibitors but also by tyrosine kinase i
nhibitors. In cell-free lysates, the GTP-gamma-S-dependent activation
of PLD was stimulated by ATP-Mg2+. This stimulation by ATP-Mg2+ did no
t respond to phorbol ester nor was it inhibited by PKC inhibitors, but
was fully restrained by tyrosine kinase inhibitors. The results sugge
st that protein phosphorylation reactions by PKC and tyrosine kinase m
ay take part, possibly in this order, in the small G-protein-coupled P
LD activation. (C) 1995 Academic Press, Inc.