Characterization of Two Alternately Spliced Forms of Phospholipase D1

Hammond, Scott M.; Jenco, John M.; Nakashima, Shigeru; Cadwallader, Karen A.; Gu, Qu Ming; Cook, Simon J.; Nozawa, Yoshinori; Prestwich, Glenn D.; Frohman, Michael A.; Morris, Andrew J.

doi:10.1074/jbc.272.6.3860

Cited by 516 publications

(379 citation statements)

References 46 publications

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“…Rho protein and protein kinase C, direct regulators of PLD1 [15], have already been identified as regulators of exocytosis from mast cells [7]. In the present study we have examined the requirement for ARF1 in antigen-stimulated exocytosis from cultured mast cells.…”

Section: Introductionmentioning

confidence: 99%

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Activation of exocytosis by cross-linking of the IgE receptor is dependent on ADP-ribosylation factor 1-regulated phospholipase D in RBL-2H3 mast cells: evidence that the mechanism of activation is via regulation of phosphatidylinositol 4,5-bisphosphate synthesis

Way

O'luanaigh

Cockcroft³

2000

Biochem. J.

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The physiological stimulus to exocytosis in mast cells is the crosslinking of the high-affinity IgE receptor, FcεR1, with antigen. We demonstrate a novel function for ADP-ribosylation factor 1 (ARF1) in the regulation of antigen-stimulated secretion using cytosol-depleted RBL-2H3 mast cells for reconstitution of secretory responses. When antigen is used as the stimulus, ARF1 also reconstitutes phospholipase D activation. Using ethanol to divert the phosphatidic acid (the product of phospholipase D activity) to phosphatidylethanol causes inhibition of ARF1-reconstituted secretion. In addition. ARF1 causes an increase in phosphatidylinositol 4,5-bisphosphate (PIP # ) levels at the expense of phosphatidylinositol 4-monophosphate. The requirement for

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Section: Introductionmentioning

confidence: 99%

“…Two mammalian PLD enzymes (PLD1 and PLD2) have been cloned [13,14]. Regulation of PLD1 has been intensively studied and is known to be directly and synergistically regulated by ARF1, Rho proteins (RhoA, Rac and Cdc42) and protein kinase Cα [15,16].…”

Section: Introductionmentioning

confidence: 99%

Activation of exocytosis by cross-linking of the IgE receptor is dependent on ADP-ribosylation factor 1-regulated phospholipase D in RBL-2H3 mast cells: evidence that the mechanism of activation is via regulation of phosphatidylinositol 4,5-bisphosphate synthesis

Way

O'luanaigh

Cockcroft³

2000

Biochem. J.

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“…Regarding the PKC regulation of PLD1 activity, both phosphorylation-dependent (23,24) and -independent mechanisms (5,25,26) have been proposed. A protein-protein interaction rather than phosphorylation has been proposed as the main mechanism for PKC␣ to activate PLD1 (26).…”

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confidence: 99%

Regulation of Phospholipase D2 Activity by Protein Kinase Cα

Chen

Exton

2004

Journal of Biological Chemistry

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It has been well documented that protein kinase C (PKC) plays an important role in regulation of phospholipase D (PLD) activity. Although PKC regulation of PLD1 activity has been studied extensively, the role of PKC in PLD2 regulation remains to be established. In the present study it was demonstrated that phorbol 12-myristate 13-acetate (PMA) induced PLD2 activation in COS-7 cells. PLD2 was also phosphorylated on both serine and threonine residues after PMA treatment. PKC inhibitors Ro-31-8220 and bisindolylmaleimide I inhibited both PMA-induced PLD2 phosphorylation and activation. However, Gö 6976, a PKC inhibitor relatively specific for conventional PKC isoforms, almost completely abolished PLD2 phosphorylation by PMA but only slightly inhibited PLD2 activation. Furthermore, time course studies showed that phosphorylation of PLD2 lagged behind its activation by PMA. Concentration curves for PMA action on PLD2 phosphorylation and activation also showed that PLD2 was activated by PMA at concentrations at which PMA didn't induce phosphorylation. A kinase-deficient mutant of PKC␣ stimulated PLD2 activity to an even higher level than wild type PKC␣. Co-expression of wild type PKC␣, but not PKC␦, greatly enhanced both basal and PMA-induced PLD2 phosphorylation. A PKC␦-specific inhibitor, rottlerin, failed to inhibit PMA-induced PLD2 phosphorylation and activation. Co-immunoprecipitation studies indicated an association between PLD2 and PKC␣ under basal conditions that was further enhanced by PMA. Time course studies of the effects of PKC␣ on PLD2 showed that as the phosphorylation of PLD2 increased, its activity declined. In summary, the data demonstrated that PLD2 is activated and phosphorylated by PMA and PKC␣ in COS-7 cells. However, the phosphorylation is not required for PKC␣ to activate PLD2. It is suggested that interaction rather than phosphorylation underscores the activation of PLD2 by PKC in vivo and that phosphorylation may contribute to the inactivation of the enzyme.Phospholipase D (PLD) 1 catalyzes the hydrolysis of phosphatidylcholine (PC) to phosphatidic acid (PA), and choline (1). PA is an important "second messenger" in several physiological processes (2). PA can be further metabolized to diacylglycerol by PA phosphohydrolase or to lysophosphatidic acid by phospholipase A2. Diacylglycerol is a well known activator of protein kinase C (PKC), whereas lysophosphatidic acid mediates many important physiological functions via its G protein-coupled receptors (3). Thus, PLD influences many important intracellular events via producing these downstream products. PLD activity is regulated by many stimuli such as growth factors, cytokines, hormones, neurotransmitters, and other molecules involved in extracellular communication (1). PLD is thought to play an important role in secretion, membrane trafficking, cytoskeleton reorganization, and apoptosis (1).PLD1 and PLD2 are two isoforms of mammalian PLD that share about 50% amino acid similarity. However, their regulatory properties are quite different, e.g. t...

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“…Some reports suggest that phosphoinositides can directly activate PLD [36]. PI 3-kinases have been shown to regulate the activity of the Ras-related low-molecular-mass GTPases Rab5 and Rab7, which have been shown to have roles in endocytosis and transport from early to late endocytic compartments [37,38].…”

Section: Discussionmentioning

confidence: 99%

“…It has also been suggested that there may be a role for isoforms of protein kinase C (PKC) in endocytosis and membrane trafficking [45]. Isoforms of PKC have been shown to be activated by, and to associate with, PI 3-kinases [46][47][48], and, in turn, PKC isoforms have been shown to activate PLD [36,49]. It is therefore conceivable that PI 3-kinase activates PLD in this system by the intermediate activation of low-molecular-mass GTPases and\or PKC isoforms.…”

Section: Discussionmentioning

confidence: 99%

Endocytosis and vesicular trafficking of immune complexes and activation of phospholipase D by the human high-affinity IgG receptor requires distinct phosphoinositide 3-kinase activities

Gillooly

Melendez

Hockaday

et al. 1999

Biochemical Journal

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FcγRI, the human high-affinity IgG receptor, is responsible for the internalization of immune complexes and their subsequent targetting to the lysosomes for degradation. We show here that aggregation of FcγRI by surface immune complexes in interferon-γ-primed U937 cells causes the transient appearance of swollen vacuolar structures, probably swollen late endosomes, which disappear as the immune complexes are degraded. Wortmannin and LY294002, specific inhibitors of phosphoinositide 3-kinases (PI 3-kinases), delay the disappearance of these structures and also correspondingly inhibit degradation of FcγRI-mediated immune complexes. In addition these inhibitors delay the initial phase of FcγRI-mediated endocytosis of immune complexes and block the activity of FcγRI-stimulated phospholipase D, an enzyme that has previously been implicated in membrane-trafficking events. p85 is the regulatory subunit of PI 3-kinase. A p85-dependent PI 3-kinase was shown to be involved in the initial phase of FcγRI-mediated endocytosis, but not in the trafficking of immune complexes for degradation or the activation of phospholipase D. The results presented here show a role for a p85-independent PI 3-kinase in regulating the trafficking of FcγRI-mediated immune complexes, either directly or as a result of the activation of phospholipase D, and a distinct role for a p85-dependent PI 3-kinase isoform in the initial phases of FcγRI-mediated internalization of immune complexes.

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Characterization of Two Alternately Spliced Forms of Phospholipase D1

Cited by 516 publications

References 46 publications

Activation of exocytosis by cross-linking of the IgE receptor is dependent on ADP-ribosylation factor 1-regulated phospholipase D in RBL-2H3 mast cells: evidence that the mechanism of activation is via regulation of phosphatidylinositol 4,5-bisphosphate synthesis

Activation of exocytosis by cross-linking of the IgE receptor is dependent on ADP-ribosylation factor 1-regulated phospholipase D in RBL-2H3 mast cells: evidence that the mechanism of activation is via regulation of phosphatidylinositol 4,5-bisphosphate synthesis

Regulation of Phospholipase D2 Activity by Protein Kinase Cα

Endocytosis and vesicular trafficking of immune complexes and activation of phospholipase D by the human high-affinity IgG receptor requires distinct phosphoinositide 3-kinase activities

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