Enhancement of lysophosphatidic acid-induced ERK phosphorylation by phospholipase D1 via the formation of phosphatidic acid

Biochem Biophys Res Commun. 2001 Mar;281(5):1337-42. doi: 10.1006/bbrc.2001.4517.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Butanols / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Genetic Vectors
  • Indoles / pharmacology
  • Lysophospholipids / pharmacology*
  • Maleimides / pharmacology
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism*
  • Pertussis Toxin
  • Phosphatidic Acids / biosynthesis*
  • Phospholipase D / antagonists & inhibitors
  • Phospholipase D / genetics
  • Phospholipase D / metabolism*
  • Phosphorylation
  • Transfection
  • Virulence Factors, Bordetella / pharmacology


  • Butanols
  • Enzyme Inhibitors
  • Indoles
  • Lysophospholipids
  • Maleimides
  • Phosphatidic Acids
  • Virulence Factors, Bordetella
  • Pertussis Toxin
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Phospholipase D
  • phospholipase D1
  • bisindolylmaleimide I