Generation of phosphorylcholine as an essential event in the activation of Raf-1 and MAP-kinases in growth factors-induced mitogenic stimulation

J Cell Biochem. 1995 Jan;57(1):141-9. doi: 10.1002/jcb.240570114.

Abstract

Cell proliferation is regulated by an appropriate combination of intracellular signals involving activation of kinases and the generation of phospholipid metabolites. We report here that growth factors induce a biphasic generation of phosphorylcholine (PCho) in quiescent NIH 3T3 cells, resulting in an early and transient increase at 100 s and a larger and sustained increase after 3 h of stimulation. Generation of PCho at both early and late times of growth factors stimulation results from the consecutive activation of phospholipase D (PLD) and choline kinase (ChoK). Production of PCho by specific growth factors seems an essential requirement for the early signals associated to activation of Raf-1 and MAP kinases, since blockage of choline kinase completely inhibited activation of Raf-1 and MAP kinases by PDGF or FGF. Both the transient early increase and the late sustained increase in PCho are required for the induction of DNA-synthesis, besides completion of the activation of the serine/threonine kinases cascade. Thus, our results strongly suggest that generation of PCho by the PLD/choline kinase pathway is one of the critical steps in regulating cell growth in NIH 3T3 stimulated by growth factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / enzymology
  • 3T3 Cells / physiology
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Enzyme Activation
  • Humans
  • Mice
  • Mitogens / pharmacology
  • Phosphorylcholine / metabolism*
  • Platelet-Derived Growth Factor / metabolism*
  • Platelet-Derived Growth Factor / pharmacology
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-raf
  • S Phase

Substances

  • Mitogens
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins
  • Phosphorylcholine
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Calcium-Calmodulin-Dependent Protein Kinases