title: Phospholipase D overcomes cell cycle arrest induced by high-intensity Raf signaling.
abstract: Low level expression of an active Raf kinase results in a transformed phenotype; however, high intensity Raf signals block cell cycle progression. Phospholipase D (PLD) has been implicated in regulating cell cycle progression and PLD activity is elevated in Raf transformed cells. We report here that high intensity Raf signals reduce PLD activity and that elevated expression of either PLD1 or PLD2 prevents cell cycle arrest induced by high intensity Raf signals. Overexpression of either PLD1 or PLD2 also reversed increases in p21(Cip1) and protein kinase C delta (PKC delta) cleavage seen with high intensity Raf signals. These data indicate that PLD signaling provides a novel survival signal that overcomes cell cycle arrest induced by high intensity Raf signaling.
authors.affiliation: Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10021, USA.
authors.forename: Troy
authors.initials: T
authors.lastname: Joseph
authors.forename: Annika
authors.initials: A
authors.lastname: Bryant
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.forename: Roger
authors.initials: R
authors.lastname: Wooden
authors.forename: Eugen
authors.initials: E
authors.lastname: Kerkhoff
authors.forename: Ulf R
authors.initials: UR
authors.lastname: Rapp
authors.forename: David A
authors.initials: DA
authors.lastname: Foster
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D010739:Phospholipase D / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000502:physiology*; D011960:Receptors, Estrogen / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D007527:Isoenzymes; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; C497259:Prkcd protein, mouse; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1