Regulation of cell survival by lipid phosphate phosphatases involves the modulation of intracellular phosphatidic acid and sphingosine 1-phosphate pools

• DOI: 10.1042/bj20050342
• Publication Date: 2005-09-26T14:46:34Z
• Authors: Jaclyn Long; Peter Darroch; Kah Fei Wan; Kok Choi Kong; Nicholas Ktistakis; Nigel J. Pyne; Susan Pyne
• Keywords: Sphingolipid

We have shown previously that LPPs (lipid phosphate phosphatases) reduce the stimulation of p42/p44 MAPK (p42/p44 mitogen-activated protein kinase) pathway by GPCR (G-protein-coupled receptor) agonists S1P (sphingosine 1-phosphate) and LPA (lysophosphatidic acid) in serum-deprived HEK-293 cells [Alderton, Darroch, Sambi, McKie, Ahmed, N. J. Pyne S. (2001) Biol. Chem. 276, 13452-13460]. In present study, we now show this can be blocked pretreating with caspase 3/7 inhibitor, Ac-DEVD-CHO [N-acetyl-Asp-Glu-Val-Asp-CHO (aldehyde)]. Therefore LPP2 LPP3 appear to regulate apoptotic status cells. This was supported further by: (i) 3/7-catalysed cleavage PARP [poly(ADP-ribose) polymerase] increased LPP2-overexpressing compared vector-transfected cells; (ii) LPP2- LPP3-overexpressing exhibited limited intranucleosomal DNA laddering, which absent Moreover, reduced basal intracellular phosphatidic acid levels, whereas decreased are constitutively co-localized SK1 kinase 1) cytoplasmic vesicles but not prevents from being recruited a perinuclear compartment upon induction PLD1 (phospholipase D1) CHO (Chinese-hamster ovary) Taken together, these data consistent an important role for regulating pool PA respectively, may govern cell serum deprivation.