Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and sphingolipid phosphate esters

Lipid phosphate phosphohydrolase (LPP)-1 cDNA was cloned from a rat liver c DNA library. It codes for a 32-kDa protein that shares 87 and 82% amino aci d sequence identities with putative products of murine and human LPP-1 cDNA s, respectively. Membrane fractions of rat2 fibroblasts that stably express ed mouse or rat LPP-1 exhibited 3.1-3.6-fold higher specific activities for phosphatidate dephosphorylation compared with vector controls. Increases i n the dephosphorylation of phosphosphatidate, ceramide 1-phosphate, sphingo sine 1-phosphate and diacylglycerol pyrophosphate were similar to those for phosphatidate. Rat2 fibroblasts expressing mouse LPP-1 cDNA showed 1.6-2.3 -fold increases in the hydrolysis of exogenous lysophosphatidate, phosphati date and ceramide 1-phosphate compared with vector control cells. Recombina nt LPP-1 was located partially in plasma membranes with its C-terminus on t he cytosolic surface. Lysophosphatidate dephosphorylation was inhibited by extracellular Ca2+ and this inhibition was diminished by extracellular Mg2. Changing intracellular Ca2+ concentrations did not alter exogenous lysoph osphatidate dephosphorylation significantly. Permeabilized fibroblasts show ed relatively little latency for the dephosphorylation of exogenous lysopho sphatidate. LPP-1 expression decreased the activation of mitogen-activated protein kinase and DNA synthesis by exogenous lysophosphatidate. The produc t of LPP-1 cDNA is concluded to act partly to degrade exogenous lysophospha tidate and thereby regulate its effects on cell signalling.