Involvement of phospholipase D in insulin-like growth factor-I-induced activation of extracellular signal-regulated kinase, but not phosphoinositide 3-kinase or Akt, in Chinese hamster ovary cells

Biochem J. 2003 Jan 15;369(Pt 2):363-8. doi: 10.1042/BJ20021368.

Abstract

Available evidence suggests the involvement of phospholipase D (PLD) in cell proliferation and survival. Phosphoinositide 3-kinase (PI 3-kinase)/Akt and extracellular signal-regulated kinases (ERKs) are signalling molecules that have essential roles in cell proliferation and survival. We previously demonstrated that sphingosine 1-phosphate (S1P)-induced PLD activation via the G-protein-coupled receptor endothelial differentiation gene (EDG) 3/S1P(3) was involved in S1P-induced stimulation of PI 3-kinase and Akt. In the present study, we examined the involvement of two PLD isozymes, PLD1 and PLD2, in insulin-like growth factor (IGF)-I receptor tyrosine kinase-mediated stimulation of PI 3-kinase/Akt and ERKs. IGF-I and to a lesser degree S1P stimulated PI 3-kinase activity in Chinese hamster ovary cells overexpressing EDG3/S1P(3). IGF-I-induced ERK phosphorylation was suppressed by butan-1-ol, but not butan-2-ol, whereas no effect of butanol was observed in IGF-I-induced Akt activation in S1P(3)-overexpressing Chinese hamster ovary cells. Overexpression of wild-type PLD1 and PLD2 substantially potentiated S1P-, but not IGF-I-, induced activation of PI 3-kinase and Akt, whereas overexpression of the catalytically inactive mutant of PLD1 or PLD2 did not affect the responses to either agonist. On the other hand, overexpression of wild-type PLD1 and PLD2 potentiated IGF-I- and, to much smaller extents, S1P-induced ERK stimulation. ERK activation by IGF-I as well as S1P was dependent on Ras, but Akt activation by IGF-I was not dependent on Ras. These results suggest that PLDs are involved in growth factor regulation of at least two signalling pathways, PI 3-kinase/Akt and ERKs, depending on the class of cell-surface receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butanols / chemistry
  • Butanols / metabolism
  • CHO Cells / metabolism*
  • Cricetinae
  • Enzyme Activation
  • Enzyme Inhibitors / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Isoenzymes / metabolism
  • Lysophospholipids*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phospholipase D / genetics
  • Phospholipase D / metabolism*
  • Phosphorylation
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Receptor, IGF Type 1 / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / genetics
  • Sphingosine / metabolism
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Butanols
  • Enzyme Inhibitors
  • Isoenzymes
  • Lysophospholipids
  • Proto-Oncogene Proteins
  • sphingosine 1-phosphate
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • Phospholipase D
  • ras Proteins
  • Sphingosine