ARF1‐regulated phospholipase D in human neutrophils is enhanced by PMA and MgATP

Whatmore, Jacqueline L.; Cronin, Paul; Cockcroft, Shamshad

doi:10.1016/0014-5793(94)00930-9

Cited by 32 publications

(20 citation statements)

References 35 publications

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“…In permeabilized U937 cells (37), GTP␥S was observed to elevate the levels of polyphosphoinositides in the presence of MgATP, and either GTP␥S-or PMA-induced PLD activation was prevented by the antibody against phosphatidylinositol 4-kinase. Furthermore, neomycin, a high affinity ligand for PIP 2 , inhibited the activity of purified PLD from brain membranes (35) and GTP␥S-induced PLD activation in permeabilized HL60 cells (15), human neutrophils (17), and U937 cells (37). The results obtained in the present study also indicated that PIP 2 was required for PKC-mediated PLD activation in HL60 membranes.…”

Section: Pkc Isozymes Responsible For Activation Of Membranebound Pldsupporting

confidence: 73%

“…Recent studies have demonstrated the implication of two small GTP-binding proteins, ADP-ribosylation factor (ARF) (9,10) and Rho (11,12) in the regulation of PLD activity in several types of cells. Furthermore, in some types of cells (13)(14)(15)(16)(17)(18)(19)(20), PLD activation induced by both GTP␥S and PMA was greatly enhanced, compared with that caused by either stimulant alone. These findings suggest that PKC may play an important role in positively modulating GTP-binding protein-mediated PLD activity.…”

Section: Phospholipase D (Pld)mentioning

confidence: 99%

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Regulation of Membrane-bound Phospholipase D by Protein Kinase C in HL60 Cells

Ohguchi

Banno

Nakashima

et al. 1996

Journal of Biological Chemistry

116

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In HL60 cells, the membrane-bound phospholipase D (PLD) was stimulated by 4␤-phorbol 12-myristate 13-acetate (PMA) in the presence of the cytosolic fraction from HL60 cells or rat brain. The cytosolic factor for this PMA-induced PLD activation was subjected to purification from rat brain by sequential chromatographies. The PLD stimulating activity was found in protein kinase C (PKC) fraction containing ␣, ␤I, ␤II, and ␥ isozymes. PKC isozymes were further separated by hydroxylapatite chromatography. PKC␣ and -␤, but not ␥, isozymes were found to activate membrane-bound PLD. PKC␣ was much more effective than PKC␤ for PLD activation. Millimolar concentrations of MgATP were required for the PKC-mediated PLD activation in HL60 membranes. MgATP is utilized to maintain the levels of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) under these assay conditions. The PKC-mediated PLD activation was completely inhibited by neomycin, a high affinity ligand for PIP 2 , and this suppression was recovered by the addition of exogenous PIP 2 . Thus, these results suggest that PIP 2 is supposed to play a key role in PKCmediated PLD activity in HL60 membranes. Furthermore, PKC␣-mediated PLD activation was potentiated by the addition of recombinant RhoA protein in the presence of guanosine 5-O-(3-thiotriphosphate) (GTP␥S). The results obtained here indicate that PKC␣ and RhoA (GTP form) exert a synergistic action in the membrane-bound PLD activation in HL60 cells. Phospholipase D (PLD)1 has been recognized to play an important role in signal transduction of many types of cells. PLD hydrolyzes phosphatidylcholine (PC) to generate phosphatidic acid (PA) and choline (1). PA and its dephosphorylated product diacylglycerol are important second messengers. PLD is activated in a variety cells in response to receptor agonists, phorbol ester and Ca 2ϩ ionophore (2). Recently, it has been pointed out that several factors are required for activation of PLD. In reconstitution experiments, activation of membranebound PLD induced by phorbol 12-myristate 13-acetate (PMA) or nonhydrolyzable guanine nucleotide (GTP␥S) was observed only when cytosol and membranes were present (3). Similar findings were obtained in permeabilized cell preparations in which leakage of cytosolic components resulted in reduction of PLD activity (4, 5). These results imply that cytosolic factors for PLD activation are involved in protein kinase C (PKC) and GTP-binding proteins.PKC has been reported to be implicated in PLD activation in various cell types. Evidence that PKC up-regulates PLD activity is supported by the observations that PKC inhibitors or PKC down-regulation by long-term exposure to PMA prevents the increase of PLD activity (2). Recently, a role for specific PKC isozymes in the regulation of PLD is presented by the studies overexpressing PKC␣ or -␤ isozymes in cells. Overexpression of PKC␤I enhances PMA-induced PLD activity in rat fibroblasts (6). Overexpression of PKC␣ in Swiss-3T3 fibroblasts (7) does not induce an acute stimulation of PLD by PMA, but rath...

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Section: Pkc Isozymes Responsible For Activation Of Membranebound Pldsupporting

confidence: 73%

Section: Phospholipase D (Pld)mentioning

confidence: 99%

Regulation of Membrane-bound Phospholipase D by Protein Kinase C in HL60 Cells

Ohguchi

Banno

Nakashima

et al. 1996

Journal of Biological Chemistry

116

View full text Add to dashboard Cite

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“…Though GTP␥S-dependent PLD has not been purified to homogeneity, an ARF-dependent PLD activated by ARFs has been characterized (18,31). Evidence also suggest that PMA-mediated responses may be dependent on the presence of ARF1 (32). The observation that PMA-pretreatment greatly enhances the ARF-dependent PLD activity suggests the recruitment of additional cytosolic components to the membranes.…”

Section: Variations Of Arf Content In Hl-60 Membranes Followingmentioning

confidence: 99%

ADP-ribosylation Factor Translocation Correlates with Potentiation of GTPγS-stimulated Phospholipase D Activity in Membrane Fractions of HL-60 Cells

Houle

Kahn

Naccache

et al. 1995

Journal of Biological Chemistry

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Phospholipase D (PLD) activation by guanine nucleotides requires protein cofactors from both the membrane and the cytosol. The small GTP-binding protein ADP-ribosylation factor (ARF) has been established as one important component of PLD activation. By stimulating HL-60 cells with various agonists and then isolating the membrane fraction and assaying PLD activity in the presence and absence of GTP␥S, we observed that fMet-Leu-Phe (fMLP) and phorbol esters induced a potentiation of GTP␥S-stimulated PLD activity in the membrane fractions of these cells. Inactive phorbol esters induced no such potentiation. Both fMLP and active phorbol esters induced a 2-3-fold increase in GTP␥S-stimulated PLD in HL-60 membranes. Membranes derived from stimulated HL-60 cells contained 60 -70% more ARF as compared with membranes derived from control cells. Membrane contents of ARF were assessed by Western blotting with the anti-ARF monoclonal antibody 1D9 followed by densitometric evaluation. Therefore, ARF translocation correlates with the potentiation of the GTP␥S-stimulated PLD activity. The effect on PLD activity and ARF membrane content achieved through fMLP stimulation was greatly enhanced by prior treatment of the cells with cytochalasin B. Membranes derived from control and fMLP-stimulated cells were assayed for PLD activity in the presence of exogenous ARF and a 50-kDa fraction known to contain elements implicated in PLD activation. The ability of ARF and the 50-kDa fraction to enhance GTP␥S-sensitive PLD activity was significantly reduced when the membranes were derived from fMLP-stimulated cells. The data indicate that, in addition to ARF, elements of the 50-kDa PLD-inducing factors were likely already translocated to the membranes upon stimulation. We propose that ARF, upon stimulation with agonists such as fMLP or phorbol esters, is translocated to the membrane and in concert with other protein components of the 50-kDa fraction enhances PLD activity.Neutrophils exercise their functions in primary host defense against pathogens through different effector systems including superoxide generation and granular secretion. It is now generally accepted that phospholipases are implicated in the generation of second messengers essential to these effector systems (1). Phospholipase C catalyzes the hydrolysis of phosphatidylinositol 4,5-biphosphate into inositol 1,4,5-triphosphate and diradylglycerol; two important second messengers. PLD 1 hydrolyzes phosphatidylcholine into choline and phosphatidic acid. Phosphatidic acid is possibly involved in superoxide anion production by inducing the dissociation of the Rac-GDP/GTP dissociation inhibitor complex (2), thereby releasing Rac, which can then assemble the NADPH oxidase complex (e.g. for review see Ref.3). Phosphatidic acid can also be converted to diradylglycerol by the enzyme phosphatidic acid phosphatase. Diradylglycerol derived from the PLD and phospholipase C pathways has been shown to cause different patterns of protein kinase C isoform translocation and to have distinct cell...

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“…In human PMNs and PMN-like cell lines, Arf1 and Arf6 are expressed and are recruited to the membrane fraction after fMLF stimulation (4,9,10), and both of them control PLD activity (11,12). The N-terminal domain of PLD is necessary for activation by Arfs (13,14).…”

mentioning

confidence: 99%

Cytohesin-1 Regulates the Arf6-Phospholipase D Signaling Axis in Human Neutrophils: Impact on Superoxide Anion Production and Secretion

Azreq

Garceau

Harbour

et al. 2009

The Journal of Immunology

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Polymorphonuclear neutrophil (PMN) stimulation with fMLP stimulates small G proteins such as ADP-ribosylation factors (Arfs) Arf1 and Arf6, leading to phospholipase D (PLD) activation and functions such as degranulation and the oxidative burst. However, the molecular links between fMLF receptors and PLD remain unclear. PMNs express cytohesin-1, an Arf-guanine exchange factor that activates Arfs, and its expression is strongly induced during the acquisition of the neutrophilic phenotype by neutrophil-like cells. The role of cytohesin-1 in the activation of the fMLF-Arf-PLD signaling axis, and the accomplishment of superoxide anion production, and degranulation was investigated in PMNs using the selective inhibitor of cytohesin, Sec 7 inhibitor H3 (secinH3). Cytohesin-1 inhibition with secinH3 leads to Arf6 but not Arf1 inhibition, demonstrating the specificity for Arf6, and fMLF-mediated activation of PLD and of the oxidative burst as well. We observed a decrease in fMLF-mediated protein secretion and expression of cell surface markers corresponding to primary (CD63/myeloperoxidase), secondary (CD66/lactoferrin), and tertiary (matrix metalloproteinase-9) granules in PMNs incubated with secinH3. Similarly, silencing cytohesin-1 or Arf6 in PLB-985 cells negatively affected fMLF-induced activation of PLD, superoxide production, and expression of granule markers on the cell surface. In contrast, stable overexpression of cytohesin-1 in PLB-985 cells enhanced fMLF-induced activation of Arf6, PLD, and NADPH oxidase. The results of this study provide evidence for an involvement of cytohesin-1 in the regulation of the functional responses of human PMNs and link these events, in part at least, to the activation of Arf6.

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ARF1‐regulated phospholipase D in human neutrophils is enhanced by PMA and MgATP

Cited by 32 publications

References 35 publications

Regulation of Membrane-bound Phospholipase D by Protein Kinase C in HL60 Cells

Regulation of Membrane-bound Phospholipase D by Protein Kinase C in HL60 Cells

ADP-ribosylation Factor Translocation Correlates with Potentiation of GTPγS-stimulated Phospholipase D Activity in Membrane Fractions of HL-60 Cells

Cytohesin-1 Regulates the Arf6-Phospholipase D Signaling Axis in Human Neutrophils: Impact on Superoxide Anion Production and Secretion

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