Pulmonary lipid phosphate phosphohydrolase in plasma membrane signalling platforms.
Lipid phosphate phosphohydrolase (LPP) has recently been proposed to have roles in signal transduction, acting sequentially to phospholipase D (PLD) and in attenuating the effects of phospholipid growth factors on cellular proliferation. In this study, LPP activity is reported to be enriched in lipid-rich signalling platforms isolated from rat lung tissue, isolated rat type II cells and type II cell-mouse lung epithelial cell lines (MLE12 and MLE15). Lung and cell line caveolin-enriched domains (CEDs), prepared on the basis of their detergent-insolubility in Triton X-100, contain caveolin-1 and protein kinase C isoforms. The LPP3 isoform was predominantly localized to rat lung CEDs. These lipid-rich domains, including those from isolated rat type II cells, were enriched both in phosphatidylcholine plus sphingomyelin (PC+SM) and cholesterol. Saponin treatment of MLE15 cells shifted the LPP activity, cholesterol, PC+SM and caveolin-1 from lipid microdomains to detergent-soluble fractions. Elevated LPP activity and LPP1/1a protein are present in caveolae from MLE15 cells prepared using the cationic-colloidal-silica 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 caveolin-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 signalling and caveolar dynamics.
Nanjundan
M
M
Department of Biochemistry, Health Sciences Building, The University of Western Ontario, London, ON, Canada N6A 5C1.
Possmayer
F
F
D000818:Animals; D021941:Caveolae / Q000737:chemistry / Q000201:enzymology; D051242:Caveolin 1; D022461:Caveolins / Q000032:analysis; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000201:enzymology / Q000502:physiology*; D002784:Cholesterol / Q000032:analysis; D003902:Detergents; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D008563:Membrane Lipids / Q000032:analysis*; D021962:Membrane Microdomains / Q000737:chemistry / Q000201:enzymology; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000032:analysis; D051381:Rats; D020545:Respiratory Mucosa / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013109:Sphingomyelins / Q000032:analysis
C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D003902:Detergents; D007527:Isoenzymes; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D002784:Cholesterol; C112948:lipid phosphate phosphatase; D010711:Phosphatidate Phosphatase