Da. Dillon et al., MAMMALIAN MG2-INDEPENDENT PHOSPHATIDATE PHOSPHATASE (PAP2) DISPLAYS DIACYLGLYCEROL PYROPHOSPHATE PHOSPHATASE-ACTIVITY(), The Journal of biological chemistry, 272(16), 1997, pp. 10361-10366
Recent studies indicate that the metabolism of diacylglycerol pyrophos
phate (DGPP) is involved in a novel lipid signaling pathway. DGPP phos
phatases (DGPP phosphohydrolase) from Saccharomyces cerevisiae and Esc
herichia coli catalyze the dephosphorylation of DGPP to yield phosphat
idate (PA) and then catalyze the dephosphorylation of PA to yield diac
ylglycerol. We demonstrated that the Mg2+-independent form of PA phosp
hatase (PA phosphohydrolase, PAPS) purified from rat liver catalyzed t
he dephosphorylation of DGPP. This reaction was Mg2+-independent, inse
nsitive to inhibition by N-ethylmaleimide and bromoenol lactone, and i
nhibited by Mn2+ ions. PAP2 exhibited a high affinity for DGPP (K-m =
0.04 mol %). The specificity constant (V-max/K-m) for DGPP was 1.3-fol
d higher than that of Pk DGPP inhibited the ability of PAPS to dephosp
horylate PA, and PA inhibited the dephosphorylation of DGPP. Like rat
liver PAP2, the Mg2+-independent PA phosphatase activity of DGPP phosp
hatase purified hom S. cerevisiae was inhibited by lyse-PA, sphingosin
e l-phosphate, and ceramide l-phosphate. Mouse PAP2 showed homology to
DGPP phosphatases from S. cerevisiae and E. coli, especially in local
ized regions that constitute a novel phosphatase sequence motif. Colle
ctively, our work indicated that rat liver PAP2 is a member of a phosp
hatase family that includes DGPP phosphatases from S. cerevisiae and E
. coli. We propose a model in which the phosphatase activities of rat
liver PAP2 and the DGPP phosphatase of S. cerevisiae regulate the cell
ular levels of DGPP, PA, and diacylglycerol.