Please confirm you are human (Sign Up for free to never see this)
← Back to Search
Nuclear Diacylglycerol Produced By Phosphoinositide-specific Phospholipase C Is Responsible For Nuclear Translocation Of Protein Kinase C-α*
L. Neri, P. Borgatti, S. Capitani, A. Martelli
Published 1998 · Biology, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
It is well established that an independent inositide cycle is present within the nucleus, where it is involved in the control of cell proliferation and differentiation. Previous results have shown that when Swiss 3T3 cells are treated with insulin-like growth factor-I (IGF-I) a rapid and sustained increase in mass of diacylglycerol (DAG) occurs within the nuclei, accompanied by a decrease in the levels of both phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate. However, it is unclear whether or not other lipids could contribute to this prolonged rise in DAG levels. We now report that the IGF-I-dependent increase in nuclear DAG production can be inhibited by the specific phosphatidylinositol phospholipase C inhibitor 1-O-octadeyl-2-O-methyl-sn-glycero-3-phosphocholine or by neomycin sulfate but not by the purported phosphatidylcholine-phospholipase C specific inhibitor D609 or by inhibitors of phospholipase D-mediated DAG generation. Treatment of cells with 1-O-octadeyl-2-O-methyl-sn-glycero-3-phosphocholine or neomycin sulfate inhibited translocation of protein kinase C-α to the nucleus. Moreover, exposure of cells to 1-O-octadeyl-2-O-methyl-sn-glycero-3-phosphocholine, but not to D609, dramatically reduced the number of cells entering S-phase upon stimulation with IGF-I. These results suggest that the only phospholipase responsible for generation of nuclear DAG after IGF-I stimulation of 3T3 cells is PI-PLC. When this activity is inhibited, neither DAG rise is seen nor PKC-α translocation to the nucleus occurs. Furthermore, this PI-PLC activity appears to be essential for the G0/G1to S-phase transition.
This paper references
Inositol trisphosphate and calcium signalling
M. Berridge (1993)
A phosphatidylcholine phospholipase C inhibitor, D609, blocks interleukin-3 (IL-3)-induced bcl-2 expression but not c-myc expression in human IL-3-dependent cells.
R. A. Mufson (1998)
Selective nuclear translocation of protein kinase C α in Swiss 3T3 cells treated with IGF‐I, PDGF and EGF
L. Neri (1994)
Nuclear Diacylglycerol and Protein Kinase C Translocation 29744 by gest on
A. M. Martelli (1989)
Inositides and the nucleus and inositides in the nucleus
N. Divecha (1993)
Protein kinase C and lipid signaling for sustained cellular responses
Y. Nishizuka (1995)
Essential role for nuclear phospholipase C beta1 in insulin-like growth factor I-induced mitogenesis.
L. Manzoli (1997)
Changes in the components of a nuclear inositide cycle during differentiation in murine erythroleukaemia cells.
N. Divecha (1995)
Phosphatidylcholine-specific Phospholipase C Regulates Thapsigargin-induced Calcium Influx in Human Lymphocytes*
J. Nofer (1997)
A New Phospholipase C 4 Is Induced at S-phase of the Cell Cycle and Appears in the Nucleus (*)
N. Liu (1996)
Temporal changes in intracellular distribution of protein kinase C in Swiss 3T3 cells during mitogenic stimulation with insulin-like growth factor I and bombesin: translocation to the nucleus follows rapid changes in nuclear polyphosphoinositides.
A. Martelli (1991)
Diacylglycerol and Phosphatidate Generated by Phospholipases C and D, Respectively, Have Distinct Fatty Acid Compositions and Functions
T. Pettitt (1997)
Nuclear diacylglycerol is increased during cell proliferation in vivo.
H. Banfić (1993)
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
U. Laemmli (1970)
Choline phospholipids: signal transduction and carcinogenesis.
S. Zeisel (1993)
Phosphorylcholine: a novel second messenger essential for mitogenic activity of growth factors.
A. Cuadrado (1993)
Alpha-thrombin-induced nuclear sn-1,2-diacylglycerols are derived from phosphatidylcholine hydrolysis in cultured fibroblasts.
M. Jarpe (1994)
Regulation of Phosphoinositide-specific Phospholipase C Isozymes*
S. Rhee (1997)
A Phospholipase D-mediated Pathway for Generating Diacylglycerol in Nuclei from Madin-Darby Canine Kidney Cells (*)
M. Balboa (1995)
Sphingomyelin Synthase, a Potential Regulator of Intracellular Levels of Ceramide and Diacylglycerol during SV40 Transformation
C. Luberto (1998)
Nuclear Phospholipase D in Madin-Darby Canine Kidney Cells
M. Balboa (1995)
Nuclear localization and signalling activity of phosphoinositidase Cβ in Swiss 3T3 cells
A. Martelli (1992)
Phospholipase D-mediated diradylglycerol formation coincides with H2O2 and lactoferrin release in adherent human neutrophils.
S. Suchard (1994)
Nuclear Diacylglycerol and Protein Kinase C Translocation 29744 by gest on A uust 31
A. M. Martelli (1989)
Phosphoinositide signaling in nuclei of Friend cells: phospholipase C beta down-regulation is related to cell differentiation.
A. Martelli (1994)
A Role for Nuclear Phosphatidylinositol-specific Phospholipase C in the G2/M Phase Transition*
B. Sun (1997)
Dependence of intracellular signaling and neurosecretion on phospholipase D activation in immortalized gonadotropin-releasing hormone neurons.
L. Zheng (1997)
New Developments in Phospholipase D*
J. Exton (1997)
Activation of type D phospholipase by serum stimulation and ras-induced transformation in NIH3T3 cells.
A. Carnero (1994)
Mitogen-stimulated phosphorylation of nuclear proteins in Swiss 3T3 cells: evidence for a protein kinase C requirement.
A. Martelli (1989)
Nuclear Diacylglycerol and Protein Kinase C Translocation 29744 by gest on O cber 3, 2017 hp://w w w .jb.org/ D
A. M. Martelli (1989)
Changes of Nuclear PI-PLC γ1 During Rat Liver Regeneration
Luca M. Neri (1997)
Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C.
Y. Nishizuka (1992)
A differential location of phosphoinositide kinases, diacylglycerol kinase, and phospholipase C in the nuclear matrix.
B. Payrastre (1992)
Phosphatidylglycerol Is a Physiologic Activator of Nuclear Protein Kinase C*
N. Murray (1998)
Mapping replicational sites in the eucaryotic cell nucleus
H. Nakayasu (1989)
Alpha-thrombin stimulates nuclear diglyceride levels and differential nuclear localization of protein kinase C isozymes in IIC9 cells.
K. Leach (1992)
Interleukin 1 alpha stimulates nuclear phospholipase C in human osteosarcoma SaOS-2 cells.
S. Marmiroli (1994)
Crosstalk among multiple signal-activated phospholipases.
M. Liscovitch (1992)
Phosphatidylcholine breakdown and signal transduction.
J. Exton (1994)
Methods in inositide research
S. Watson (1991)
Nuclear Translocation of RhoA Mediates the Mitogen-induced Activation of Phospholipase D Involved in Nuclear Envelope Signal Transduction*
J. Baldassare (1997)
This paper is referenced by
Cell Signaling through Protein Kinase C Oxidation and Activation
Daniela Cosentino-Gomes (2012)
Insulin-related signaling pathways elicited by light in photoreceptor nuclei from bovine retina.
P. M. Natalini (2016)
Proliferating or differentiating stimuli act on different lipid-dependent signaling pathways in nuclei of human leukemia cells.
L. Neri (2002)
Insulin-Like Growth Factor I Kinase Mediates the Mitogenic Action of 1 by Extracellular Signal-Regulated β C Phosphorylation of Nuclear Phospholipase
PIKE GTPase Signaling and Function
J. Ahn (2005)
Binding of elements of protein kinase C-α regulatory domain to lamin B1
G. Tabellini (2002)
Re-examination of the significance of nuclear localization of PLCbeta1 in the likelihood of its involvement in neoplastic cell growth.
L. Cocco (2003)
Nuclear protein kinase C isoforms: key players in multiple cell functions?
A. Martelli (2003)
Nuclear envelope rupture and NET formation is driven by PKCα‐mediated lamin B disassembly
Y. Li (2020)
The roles of PIKE in tumorigenesis
Q. Qi (2013)
PIKE GTPase: a novel mediator of phosphoinositide signaling
K. Ye (2004)
Nuclear inositol lipid signaling.
L. Cocco (2001)
Advances in Brief Enhanced Nuclear Diacylglycerol Kinase Activity in Response to a Mitogenic Stimulation of Quiescent Swiss 3 T 3 Cells with Insulin-like Growth Factor I 1
A. Martelli (2000)
Phosphoinositides in Subcellular Targeting and Enzyme Activation
H. Stenmark (2004)
Spontaneous calcium oscillations and nuclear PLC‐β1 in human GV oocytes
F. Miyara (2008)
Nuclear lipid signalling
R. Irvine (2003)
Increase of Nuclear Ceramide through Caspase-3-Dependent Regulation of the “Sphingomyelin Cycle” in Fas-Induced Apoptosis
Mitsumasa Watanabe (2004)
Phospholipase C-δ1 Contains a Functional Nuclear Export Signal Sequence*
M. Yamaga (1999)
Nuclear phosphoinositides and their functions.
G. Hammond (2004)
Phosphatidylcholine Metabolism in Nuclei of Phorbol Ester-Activated LA-N-1 Neuroblastoma Cells
P. Antony (2004)
Phosphatidylinositol 3‐Kinase Translocates to the Nucleus of Osteoblast‐Like MC3T3‐E1 Cells in Response to Insulin‐Like Growth Factor I and Platelet‐Derived Growth Factor But Not to the Proapoptotic Cytokine Tumor Necrosis Factor α
A. Martelli (2000)
CD28 co‐stimulates TCR/CD3‐induced phosphoinositide turnover in human T lymphocytes
R. Zaru (2001)
Nuclear Lipid Signaling
R. Irvine (2002)
Mesangial cell-reduced Ca2+ signaling in high glucose is due to inactivation of phospholipase C-beta3 by protein kinase C.
Helena Frecker (2005)
TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest.
C. Evangelisti (2009)
Protein kinase C--induced hypertrophy of neonatal rat ventricular myocytes
Kalpana Vijayan (2004)
PKC gamma senses/protects from stress in retina through regulation of gap junctions
V. Yevseyenkov (2010)
Nucleophosmin/B23, a nuclear PI(3,4,5)P(3) receptor, mediates the antiapoptotic actions of NGF by inhibiting CAD.
J. Ahn (2005)
PIKE GTPase-mediated nuclear signalings promote cell survival.
K. Ye (2006)
IGF-I-induced phosphorylation of connexin 43 by PKCgamma: regulation of gap junctions in rabbit lens epithelial cells.
D. Lin (2003)
Nuclear domains involved in inositol lipid signal transductionmaltese cross.
N. M. Maraldi (2000)
Re‐examination of the mechanisms regulating nuclear inositol lipid metabolism
A. Martelli (2001)See more