title: Generation of phosphorylcholine as an essential event in the activation of Raf-1 and MAP-kinases in growth factors-induced mitogenic stimulation.
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.
authors.affiliation: Instituto de Investigaciones Biomédicas, CSIC, Universidad Autónoma de Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Jiménez
authors.forename: L
authors.initials: L
authors.lastname: del Peso
authors.forename: S
authors.initials: S
authors.lastname: Montaner
authors.forename: P
authors.initials: P
authors.lastname: Esteve
authors.forename: J C
authors.initials: JC
authors.lastname: Lacal
mesh_terms: D016475:3T3 Cells / Q000201:enzymology / Q000502:physiology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D010767:Phosphorylcholine / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D016196:S Phase
chemical_list: D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D010767:Phosphorylcholine; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases