Phospholipase D overcomes cell cycle arrest induced by high-intensity Raf signaling.
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.
Joseph
Troy
T
Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10021, USA.
Bryant
Annika
A
Frankel
Paul
P
Wooden
Roger
R
Kerkhoff
Eugen
E
Rapp
Ulf R
UR
Foster
David A
DA
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
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