Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and sphingolipid phosphate esters.
Lipid phosphate phosphohydrolase (LPP)-1 cDNA was cloned from a rat liver cDNA library. It codes for a 32-kDa protein that shares 87 and 82% amino acid sequence identities with putative products of murine and human LPP-1 cDNAs, respectively. Membrane fractions of rat2 fibroblasts that stably expressed mouse or rat LPP-1 exhibited 3.1-3. 6-fold higher specific activities for phosphatidate dephosphorylation compared with vector controls. Increases in the dephosphorylation of lysophosphatidate, ceramide 1-phosphate, sphingosine 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, phosphatidate and ceramide 1-phosphate compared with vector control cells. Recombinant LPP-1 was located partially in plasma membranes with its C-terminus on the 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 lysophosphatidate dephosphorylation significantly. Permeabilized fibroblasts showed relatively little latency for the dephosphorylation of exogenous lysophosphatidate. LPP-1 expression decreased the activation of mitogen-activated protein kinase and DNA synthesis by exogenous lysophosphatidate. The product of LPP-1 cDNA is concluded to act partly to degrade exogenous lysophosphatidate and thereby regulate its effects on cell signalling.
Jasinska
R
R
Department of Biochemistry (Signal Transduction Laboratories), Lipid and Lipoprotein Research Group, University of Alberta, 357 Heritage Medical Research Centre, Edmonton, Alberta, T6G 2S2, Canada.
Zhang
Q X
QX
Pilquil
C
C
Singh
I
I
Xu
J
J
Dewald
J
J
Dillon
D A
DA
Berthiaume
L G
LG
Carman
G M
GM
Waggoner
D W
DW
Brindley
D N
DN
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002463:Cell Membrane Permeability; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D004952:Esters / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D010710:Phosphates / Q000378:metabolism*; D010711:Phosphatidate Phosphatase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism*; D013379:Substrate Specificity
D004952:Esters; D006017:Glycolipids; D008246:Lysophospholipids; D010710:Phosphates; D011993:Recombinant Fusion Proteins; D013107:Sphingolipids; C015903:glycerolglycolipids; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C112948:lipid phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases; D010711:Phosphatidate Phosphatase; D002118:Calcium