Phosphatidate degradation: Phosphatidate phosphatases (lipins) and lipid phosphate phosphatases

Abstract

SummaryThree lipid phosphate phosphatases (LPPs) regulate cell signaling by modifying the concentrations of a variety of lipid phosphates versus their dephosphorylated products. In particular, the LPPs are normally considered to regulate signaling by the phospholipase D (PLD) pathway by converting phosphatidate (PA) to diacylglycerol (DAG). LPP activities do modulate the accumulations of PA and DAG following PLD activation, but this could also involve an effect upstream of PLD activation. The active sites of the LPPs are on the exterior surface of plasma membranes, or on the luminal surface of internal membranes. Consequently, the actions of the LPPs in metabolizing PA formed by PLD1 or PLD2 should depend on the access of this substrate to the active site of the LPPs. Alternatively, PA generated on the cytosolic surface of membranes should be readily accessible to the family of specific phosphatidate phosphatases, namely the lipins. Presently, there is only indirect evidence for the lipins participating in cell signaling following PLD activation. So far, we know relatively little about how individual LPPs and specific phosphatidate phosphatases (lipins) modulate cell signaling through controlling the turnover of bioactive lipids that are formed after PLD activation.

Tetracyclines increase lipid phosphate phosphatase expression on plasma membranes and turnover of plasma lysophosphatidate

“…This is probably explained because dephosphorylation of extracellular S1P depends on the expression of LPP3, with LPP1 and LPP2 having little effect. These results indicate that although the LPPs show relatively little specifi city for different lipid phosphates when these are in detergent micelles ( 40 ), there does appear to be selectivity for the ecto-activities in intact cells. Our conclusion that LPP3 acts preferentially on extracellular S1P is compatible with studies on the dephosphorylation of FTY720-P, which is an analog of S1P.…”

Lipid phosphate phosphatases and their roles in mammalian physiology and pathology

“…Furthermore, increasing the expression of LPP1 in fi broblasts decreases the effects of LPA and platelet-derived growth factor in activating PLD, which provides an alternative explanation of the observed decrease in steady-state PA concentrations ( 60 ). Actually, the lipin family of PAPs is now thought to provide the capacity for degrading PA on the cytosolic surface of membranes ( 93 ).…”

Lipin 2 Binds Phosphatidic Acid by the Electrostatic Hydrogen Bond Switch Mechanism Independent of Phosphorylation

“…The relative PAP activity of human lipin 2 has been previously determined in cell lysates (17,18). In this study, we examine lipin 2 kinetics, first as a general characterization and then with respect to PA charge and phosphorylation.…”