A Mg2+-independent and N-ethylmaleimide-insensitive phosphatidate phos
phohydrolase (PAP-2) has been identified in the plasma membrane of cel
ls and it has been purified. The enzyme is a multi-functional phosphoh
ydrolase that can dephosphorylate phosphatidate, lysophosphatidate, sp
hingosine l-phosphate and ceramide l-phosphate and these substrates ar
e competitive inhibitors of the reaction. The action of PAP-2 could te
rminate signalling by these bioactive lipids and at the same time gene
rates compounds such as diacylglycerol, sphingosine and ceramide which
are also potent signalling molecules. In relation to phosphatidate me
tabolism, sphingosine (or sphingosine l-phosphate) stimulates phosphol
ipase D and thus the formation of phosphatidate. At the same time sphi
ngosine inhibits PAP-2 activity thus further increasing phosphatidate
concentrations. By contrast, ceramides inhibit the activation of phosp
holipase D by a wide variety of agonists and increase the dephosphoryl
ation of phosphatidate, lysophosphatidate, sphingosine l-phosphate and
ceramide l-phosphate. These actions demonstrate 'cross-talk' between
the glycerolipid and sphingolipid signalling pathways and the involvem
ent of PAP-2 in modifying the balance of the bioactive lipids generate
d by these pathways during cell activation.