Enhancement of lysophosphatidic acid-induced ERK phosphorylation by phospholipase D1 via the formation of phosphatidic acid.
We made stable cell lines overexpressing PLD1 (GP-PLD1) from GP+envAm12 cell, a derivative of NIH 3T3 cell. PLD1 activity and extracellular signal-regulated kinase (ERK) phosphorylation were enhanced in GP-PLD1 cells by the treatment of lysophosphatidic acid (LPA). In contrast, these LPA-induced effects were attenuated with the pretreatment of pertussis toxin (PTX) or protein kinase C (PKC) inhibitor. Moreover, accumulation of phosphatidic acid (PA), a product of PLD action, potentiated the LPA-induced ERK activation in GP-PLD1 cells while blocking of PA production with the treatment of 1-butanol attenuated LPA-induced ERK phosphorylation. From these results, we suggest that LPA activate PLD1 through pertussis toxin-sensitive G protein and PKC-dependent pathways, then PA produced from PLD1 activation facilitate ERK phosphorylation.
Department of Pharmacology, School of Medicine, Taejon, Korea.
J H
JH
Hong
S O
SO
Oh
M
M
Lee
Y R
YR
Kim
D U
DU
Kim
G M
GM
Hur
J H
JH
Lee
K
K
Lim
B D
BD
Hwang
S K
SK
Park
D016475:3T3 Cells; D000818:Animals; D000440:Butanols / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005822:Genetic Vectors; D007211:Indoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D037342:Pertussis Toxin; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000440:Butanols; D004791:Enzyme Inhibitors; D007211:Indoles; D008246:Lysophospholipids; D008301:Maleimides; D010712:Phosphatidic Acids; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010739:Phospholipase D; C106801:phospholipase D1; C070515:bisindolylmaleimide I