Pulmonary lipid phosphate phosphohydrolase in plasma membrane signalling platforms

Lipid phosphate phosphohydrolase (LPP) has recently been proposed to have r oles in signal transduction, acting sequentially to phospholipase D (PLD) a nd in attenuating the effects of phospholipid growth factors on cellular pr oliferation. In this study, LPP activity is reported to be enriched in lipi d-rich signalling platforms isolated from rat lung tissue, isolated rat typ e II cells and type II cell-mouse lung epithelial cell lines (MLE12 and MLE 15). Lung and cell line caveolin-enriched domains (CEDs), prepared on the b asis of their detergent-insolubility in Triton X-100, contain caveolin-1 an d protein kinase C isoforms. The LPP3 isoform was predominantly localized t o rat lung CEDs. These lipid-rich domains, including those from isolated ra t type II cells, were enriched both in phosphatidylcholine plus sphingomyel in (PC+SM) and cholesterol. Saponin treatment of MLE15 cells shifted the LP P activity, cholesterol, PC+SM and caveolin-1 from lipid micro-domains to d etergent-soluble fractions. Elevated LPP activity and LPP1/1a protein are p resent in caveolae from MLE15 cells prepared using the cationic-colloidal-s ilica method. In contrast, total plasma membranes had a higher abundance of LPP1/1a protein with low LPP activity. Phorbol ester treatment caused a 3. 8-fold increase in LPP-specific activity in MLE12 CEDs. Thus the activated form of LPP1/1a may be recruited into caveolae/ rafts. Transdifferentiation of type II cells into a type I-like cell demonstrated enrichment in caveol in-1 levels and LPP activity. These results indicate that LPP is localized in caveolae and/or rafts in lung tissue, isolated type II cells and type II cell lines and is consistent with a role for LPP in both caveolae/raft sig nalling and caveolar dynamics.