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Distinct Mechanisms Of Phospholipase D Activation And Attenuation Utilized By Different Mitogens In NIH-3T3 Fibroblasts.
P. Ben-Av, Y. Eli, U. Schmidt, K. Tobias, M. Liscovitch
Published 1993 · Biology, Medicine
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The activation of phospholipase D (PLD) by platelet-derived growth factor (PDGF), prostaglandin F2 alpha and 12-O-tetradecanoylphorbol 13-acetate (TPA) was studied in NIH-3T3 fibroblasts. PLD activation was determined by measuring the production of both [3H]phosphatidic acid and [3H]phosphatidylpropanol (products of the PLD-catalyzed hydrolysis and transphosphatidylation reactions, respectively), in cells that were metabolically pre-labeled with [3H]oleic acid. All mitogens caused a rapid (within 2 min) activation of PLD. Activation of PLD by prostaglandin F2 alpha and PDGF was transient and declined to near basal levels by 15 min and 55 min, respectively. In contrast, TPA-induced activation of PLD was sustained for at least 60 min of incubation. A combination of maximally effective concentrations of PDGF and TPA stimulated PLD activity in a non-additive manner, while the effect of prostaglandin F2 alpha was additional to that of either PDGF or TPA. The protein kinase inhibitor staurosporine inhibited PLD activation by PDGF or TPA with almost identical dose/response curves. In contrast, staurosporine potentiated prostaglandin-F2 alpha-induced PLD activation. The specific protein kinase C inhibitor GF109203X (a bisindolylmaleimide) inhibited PLD activation by prostaglandin F2 alpha and PDGF at concentrations higher than those required for inhibition of PLD activation induced by TPA. Depletion of cellular protein kinase C abolished PLD activation by all three mitogens without affecting in vitro activity of membrane-bound PLD. The distinct kinetics of PLD activation and its differential susceptibility to protein kinase inhibitors suggest the existence of agonist-specific activation and/or inactivation mechanisms. The results indicate also that protein kinase C participates in the mechanism of PLD activation via PDGF, while the effect of prostaglandin F2 alpha involves a pathway independent of protein kinase C.
This paper references
Prostaglandin receptors in NIH 3T3 cells: coupling of one receptor to adenylate cyclase and of a second receptor to phospholipase C.
F. Gusovsky (1991)
The biologically active phospholipid, lysophosphatidic acid, induces phosphatidylcholine breakdown in fibroblasts via activation of phospholipase D. Comparison with the response to endothelin.
R. L. van der Bend (1992)
Stimulation of phosphatidylcholine breakdown and diacylglycerol production by growth factors in Swiss-3T3 cells.
B. Price (1989)
Phorbol ester or diacylglycerol modulates somatostatin binding to its receptors on rat pancreatic acinar cell membranes.
T. Matozaki (1986)
Hypotonicity stimulates phosphatidylcholine hydrolysis and generates diacylglycerol in erythrocytes.
M. Musch (1990)
ATP stimulates the hydrolysis of phosphatidylethanolamine in NIH 3T3 cells. Potentiating effects of guanosine triphosphates and sphingosine.
Z. Kiss (1990)
Phospholipase C-γ is a substrate for the PDGF and EGF receptor protein-tyrosine kinases in vivo and in vitro
J. Meisenhelder (1989)
Activation of multiple mechanisms including phospholipase D by endothelin-1 in rat aorta.
Y. Liu (1992)
Signaling through phosphatidylcholine breakdown.
J. Exton (1990)
Production of phosphatidylethanol by phospholipase D phosphatidyl transferase in intact or dispersed pancreatic islets: evidence for the in situ metabolism of phosphatidylethanol.
S. Metz (1990)
Phosphatidylethanol biosynthesis in ethanol-exposed NG108-15 neuroblastoma X glioma hybrid cells. Evidence for activation of a phospholipase D phosphatidyl transferase activity by protein kinase C.
M. Liscovitch (1989)
The regulation of phospholipase D activity and its role in sn-1,2-diradylglycerol formation in bombesin- and phorbol 12-myristate 13-acetate-stimulated Swiss 3T3 cells.
S. Cook (1991)
A neutral phospholipase D activity from rat brain synaptic plasma membranes. Identification and partial characterization.
V. Chalifa (1990)
Epidermal-growth-factor-induced production of phosphatidylalcohols by HeLa cells and A431 cells through activation of phospholipase D.
M. Kaszkin (1992)
Phospholipase D activation in a cell-free system from human neutrophils by phorbol 12-myristate 13-acetate and guanosine 5'-O-(3-thiotriphosphate). Activation is calcium dependent and requires protein factors in both the plasma membrane and cytosol.
S. Olson (1991)
Phospholipase D activation by the mitogens platelet‐derived growth factor and 12‐O‐tetradecanoylphorbol 13‐acetate in NIH‐3T3 cells
P. Ben-Av (1989)
Differential effects of platelet-derived growth factor, serum and bombesin on phospholipase D-mediated hydrolysis of phosphatidylethanolamine in NIH 3T3 fibroblasts.
Z. Kiss (1992)
Phospholipase D activation in human natural killer cells through the Kp43 and CD16 surface antigens takes place by different mechanisms. Involvement of the phospholipase D pathway in tumor necrosis factor alpha synthesis
M. Balboa (1992)
v-Src increases diacylglycerol levels via a type D phospholipase-mediated hydrolysis of phosphatidylcholine.
J. Song (1991)
The regulation and cellular functions of phosphatidylcholine hydrolysis.
M. Billah (1990)
Multiple sources of sn-1,2-diacylglycerol in platelet-derived-growth-factor-stimulated Swiss 3T3 fibroblasts. Evidence for activation of phosphoinositidase C and phosphatidylcholine-specific phospholipase D.
R. Plevin (1991)
Receptor-coupled phospholipase D: regulation and functional significance.
M. Billah (1991)
Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases
U. Ruegg (1989)
Differential regulation of phosphoinositide and phosphatidylcholine hydrolysis by protein kinase C-beta 1 overexpression. Effects on stimulation by alpha-thrombin, guanosine 5'-O-(thiotriphosphate), and calcium.
J. Pachter (1992)
Cyclic AMP-elevating agents block chemoattractant activation of diradylglycerol generation by inhibiting phospholipase D activation.
S. R. Tyagi (1991)
Inositol phosphates and cell signalling
M. Berridge (1989)
Activation of phospholipase D by alpha-thrombin or epidermal growth factor contributes to the formation of phosphatidic acid, but not to observed increases in 1,2-diacylglycerol.
T. M. Wright (1992)
Kinetics of enzymes requiring long-chain acyl-CoA esters as substrates: effects of substrate binding to albumin.
K. Bartlett (1985)
Alpha 2-C10 adrenergic receptors expressed in rat 1 fibroblasts can regulate both adenylylcyclase and phospholipase D-mediated hydrolysis of phosphatidylcholine by interacting with pertussis toxin-sensitive guanine nucleotide-binding proteins.
E. E. MacNulty (1992)
Phospholipase D catalyzes phospholipid metabolism in chemotactic peptide-stimulated HL-60 granulocytes.
J. Pai (1988)
Oncogenes and signal transduction
L. Cantley (1991)
Hydrolysis of phosphatidylcholine by phospholipase D is a common response to mitogens which stimulate inositol lipid hydrolysis in Swiss 3T3 fibroblasts.
S. Cook (1991)
Receptor regulation of choline phospholipid hydrolysis. A novel source of diacylglycerol and phosphatidic acid.
K. Löffelholz (1989)
Ca2+ inhibits guanine nucleotide-activated phospholipase D in neural-derived NG108-15 cells.
M. Liscovitch (1991)
Lipid A stimulates phospholipase D activity in rat mesangial cells via a G-protein.
W. E. Harrris (1992)
Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C.
Y. Nishizuka (1992)
Regulation of inositol phospholipid-specific phospholipase C isozymes.
S. Rhee (1992)
Rapid protein kinase C-dependent activation of phospholipase D leads to delayed 1,2-diglyceride accumulation.
E. Martinson (1990)
Preparation of phospholipids and their analogs by phospholipase D.
H. Eibl (1981)
Multisite phosphorylation of the alpha subunit of transducin by the insulin receptor kinase and protein kinase C.
Y. Zick (1986)
Existence of cytosolic phospholipase D. Identification and comparison with membrane-bound enzyme.
P. Wang (1991)
Peroxides of vanadate induce activation of phospholipase D in HL-60 cells. Role of tyrosine phosphorylation.
S. Bourgoin (1992)
Nuclear localization and signalling activity of phosphoinositidase Cβ in Swiss 3T3 cells
A. Martelli (1992)
Preferential inhibition of the platelet-derived growth factor receptor tyrosine kinase by staurosporine.
J. Secrist (1990)
Phosphatidate accumulation in hormone-treated hepatocytes via a phospholipase D mechanism.
S. Bocckino (1987)
Protein measurement with the Folin phenol reagent.
O. H. Lowry (1951)
Regulation of phospholipase D-induced hydrolysis of choline-containing phosphoglycerides by cyclic AMP in human neutrophils.
D. E. Agwu (1991)
Gonadotropin-releasing hormone activates phospholipase D in ovarian granulosa cells. Possible role in signal transduction.
M. Liscovitch (1989)
Regulation of phospholipase D and primary granule secretion by P2-purinergic- and chemotactic peptide-receptor agonists is induced during granulocytic differentiation of HL-60 cells.
M. Xie (1991)
Crosstalk among multiple signal-activated phospholipases.
M. Liscovitch (1992)
Phospholipase D activation by platelet-activating factor, leukotriene B4, and formyl-methionyl-leucyl-phenylalanine in rabbit neutrophils. Phospholipase D activation is involved in enzyme release.
Y. Kanaho (1991)
Antigen-induced phospholipase D activation in rat mast cells is independent of protein kinase C.
K. Yamada (1991)
Tyrosine phosphorylation is involved in receptor coupling to phospholipase D but not phospholipase C in the human neutrophil.
I. Uings (1992)
Human brain n-chimaerin cDNA encodes a novel phorbol ester receptor.
S. Ahmed (1990)
The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.
D. Toullec (1991)
Vasopressin-induced polyphosphoinositide and phosphatidylcholine degradation in fibroblasts. Temporal relationship for formation of phospholipase C and phospholipase D hydrolysis products.
C. Huang (1990)
This paper is referenced by
Biochemistry of Signal Transduction in Myocardium
J. Lamers (1996)
Inhibition of PDGF-induced phospholipase C activation by herbimycin A.
B. Y. Kim (1996)
Mechanism of angiotensin II-induced phospholipase D activation in bovine adrenal glomerulosa cells
W. Bollag (2002)
Calcitriol transmembrane signalling: regulation of rat muscle phospholipase D activity.
M. Facchinetti (1998)
Phospholipase D and Its Product, Phosphatidic Acid, Mediate Agonist-dependent Raf-1 Translocation to the Plasma Membrane and the Activation of the Mitogen-activated Protein Kinase Pathway*
M. Rizzo (1999)
Role of phospholipase D in laminin-induced production of gelatinase A (MMP-2) in metastatic cells
R. Reich (2004)
Raf-1 Kinase Possesses Distinct Binding Domains for Phosphatidylserine and Phosphatidic Acid
S. Ghosh (1996)
Participation of phospholipase D and α/β-protein kinase C in growth factor-induced signalling in C3H10T1/2 fibroblasts
V. Thorsen (2003)
Phospholipase D, tumor promoters, proliferation and prostaglandins.
L. Daniel (1999)
Enzymology of mammalian phospholipases D: in vitro studies.
M. Liscovitch (1996)
Analysis of Platelet-derived Growth Factor-induced Phospholipase D Activation in Mouse Embryo Fibroblasts Lacking Phospholipase C-γ1*
J. Hess (1998)
Phospholipase D: role in signal transduction and membrane traffic.
M. Liscovitch (1996)
The Ang II-induced growth of vascular smooth muscle cells involves a phospholipase D-mediated signaling mechanism.
E. Freeman (2000)
Neuromedin B activates phospholipase D through both PKC-dependent and PKC-independent mechanisms.
W. Hou (1998)
Preferential inhibition of phorbol ester‐induced hydrolysis of phosphatidylethanolamine by N‐acetylsphingosine in NIH 3T3 fibroblasts
Z. Kiss (1995)
Inhibition of GTP gamma S-dependent phospholipase D and Rho membrane association by calphostin is independent of protein kinase C catalytic activity.
G. Dubyak (1997)
Effect of prostaglandin E2 on phospholipase D activity in osteoblast‐like MC3T3‐E1 cells
Y. Oiso (1995)
Pharmacology and intracellular signaling mechanisms of the native human orphan receptor BRS-3 in lung cancer cells.
R. R. Ryan (1998)
Mammalian phospholipase D structure and regulation.
M. Frohman (1999)
ARF proteins mediate insulin-dependent activation of phospholipase D
K. Shome (1997)
Phenotypic transformation of normal rat kidney fibroblasts by endothelin-1. Different mode of action from lysophosphatidic acid, bradykinin, and prostaglandin f2alpha.
D. Lahaye (1999)
Involvement of Phosphatidylcholine-specific Phospholipase C in Platelet-derived Growth Factor-induced Activation of the Mitogen-activated Protein Kinase Pathway in Rat-1 Fibroblasts*
M. V. van Dijk (1997)
Rapid and Persistent Desensitization of m3 Muscarinic Acetylcholine Receptor-stimulated Phospholipase D
M. Schmidt (1995)
Phospholipase D structure and regulation.
M. Frohman (1999)
Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization
W. C. Colley (1997)
Activation of phospholipase D by prostaglandin F2 alpha in rat luteal cells and effects of inhibitors of arachidonic acid metabolism.
H. Yamamoto (1995)
Localization of Phospholipase D in Detergent-insoluble, Caveolin-rich Membrane Domains
M. Czarny (1999)
Role of EGF-receptor density in phenotypic transformation of NRK cells
D.H.T.P. Odinot-Lahaye (2000)
Mechanisms of phospholipase D stimulation by m3 muscarinic acetylcholine receptors. Evidence for involvement of tyrosine phosphorylation.
M. Schmidt (1994)
Purinergic agonist and G protein stimulation of phospholipase D in rat liver plasma membranes. Independence from phospholipase C activation.
K. Malcolm (1995)
Stimulation of Phospholipase D by Epidermal Growth Factor Requires Protein Kinase C Activation in Swiss 3T3 Cells (*)
E. J. Yeo (1995)
PLD activation in Chinese hamster ovary (CHO) cells transfected with PGF2α receptor cDNA
B. Liu (1996)See more