Inhibition of Protein Kinase C-Dependent Noradrenaline Release by Wortmannin in PC12 Cells

Oda, Haruko; Murayama, Toshihiko; Nomura, Yasuyuki

doi:10.1006/abbi.1996.9744

Cited by 14 publications

(4 citation statements)

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“…Direct activation of PKC by phorbol esters induces PI 3-kinasedependent signaling pathways not only in neutrophils. Actin filament formation in platelets [56], cell transformation [57], DNA synthesis [58], noradrenalin release [59], as well as glucose transport in adipocytes [60], are all processes activated by PMA in a PI 3-kinase-dependent manner. The positioning of PI 3-kinase both upstream and downstream of PKC is not necessarily a contradiction.…”

Section: Discussionmentioning

confidence: 99%

Phorbol myristate acetate induces neutrophil NADPH-oxidase activity by two separate signal transduction pathways: dependent or independent of phosphatidylinositol 3-kinase

Karlsson

Nixon

McPhail

2000

Journal of Leukocyte Biology

189

124

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The neutrophil NADPH-oxidase can be activated by protein kinase C (PKC) agonists such as phorbol myristate acetate (PMA), resulting in superoxide anion release. This superoxide release is independent of phosphatidylinositol 3-kinase (PI 3-kinase) because the inhibitor wortmannin does not affect the response. In this study, PMA is shown to also induce a wortmannin-sensitive NADPHoxidase activation, however, not resulting in release of superoxide but in intracellular production of the radical. This indicates that two pools of NADPH-oxidase, one localized in the plasma membrane and the other in the granule membranes, are separately regulated and the signal transduction pathways leading to activation of these pools differ regarding involvement of PI 3-kinase. Activation of both pools was dependent on ERK/MAPK kinase (MEK) activity and protein phosphatase 1 and/or 2A. As the two oxidase responses were differently affected by the inhibitor Gö -6850, different PKC isozymes are suggested to take part in the two signal transduction pathways. J. Leukoc. Biol. 67: 396-404; 2000.

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Section: Discussionmentioning

confidence: 99%

Phorbol myristate acetate induces neutrophil NADPH-oxidase activity by two separate signal transduction pathways: dependent or independent of phosphatidylinositol 3-kinase

Karlsson

Nixon

McPhail

2000

Journal of Leukocyte Biology

189

124

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“…Phosphatidylinositol (PI) 3-kinase is a key element in transducing various actions of insulin on downstream effectors (19,20) and has been implicated in controlling vesicle trafficking and secretory function in many cell types (21)(22)(23)(24)(25)(26)(27). Pancreatic ␤-ells also contain PI 3-kinase activity (28 -30).…”

mentioning

confidence: 99%

Phosphatidylinositol 3-Kinase Suppresses Glucose-Stimulated Insulin Secretion by Affecting Post-Cytosolic [Ca2+] Elevation Signals

et al. 2002

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The role of phosphatidylinositol (PI) 3-kinase in the regulation of pancreatic ␤-cell function was investigated. PI 3-kinase activity in p85␣ regulatory subunitdeficient (p85␣ ؊/؊ ) islets was decreased to ϳ20% of that in wild-type controls. Insulin content and mass of rough endoplasmic reticula were decreased in ␤-cells from p85␣؊/؊ mice with increased insulin sensitivity. However, p85␣؊/؊ ␤-cells exhibited a marked increase in the insulin secretory response to higher concentrations of glucose. When PI 3-kinase in wild-type islets was suppressed by wortmannin or LY294002, the secretion was also substantially potentiated. Wortmannin's potentiating effect was not due to augmentation in glucose metabolism or cytosolic [Ca 2؉ ] elevation. Results of p85␣ ؊/؊ islets and wortmannin-treated wildtype islets stimulated with diazoxide and KCl showed that inhibition of PI 3-kinase activity exerted its effect on secretion, at least in part, distal to a cytosolic [Ca 2؉ ] elevation. These results suggest that PI 3-kinase activity normally plays a crucial role in the suppression of glucose-stimulated insulin secretion. Diabetes 51: 87-97, 2002

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“…In resting chromaffin LY294002 on peripheral actin, cells displaying a depocells, p85 was found essentially in the subplasmalemlymerized actin ring were counted in randomly selected mal region colocalized with filamentous actin. The P1 3-kinase activity was present in anti-p85 immunopreiting myosin light-chain kinase (Ohara-Imaizumi et al, cipitates, indicating that PT 3-kinase occurs as a hetero-1992) and/or protein kinase C-dependent pathways dimer with the catalytic subunit tightly associated with (Oda et a!., 1997). Here, we used the quercetin anap85 in the subplasmalemmal cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

Possible Involvement of Phosphatidylinositol 3‐Kinase in Regulated Exocytosis: Studies in Chromaffin Cells with Inhibitor LY294002

Chasserot‐Golaz

Hubert

Thiersé

et al. 1998

Journal of Neurochemistry

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Several lines of evidence suggest that phosaffinity for proline-rich domains and may be involved phorylated products of phosphatidylinositol play critical in the association of P1 3-kinase with cytoskeletal profunctions in the regulation of membrane trafficking along teins. The I 1O-kDa subunit of P1 3-kinase has two the secretory pathway. To probe the possible involvecatalytic activities: a Mn 2-dependent protein kinase ment of phosphatidylinositol 3-kinase (P1 3-kinase) in activity that phosphorylates p85, and a Mg2~-depenregulated exocytosis, we have examined its subcellular dent lipid kinase activity that phosphorylates the D-3 distribution in cultured chromaffin cells by immunoreplica analysis and confocal immunofluorescence. We found position of the inositol ring producing phosphatidylthat the P1 3-kinase heterodimer consisting of the regulainositol 3-phosphate, phosphatidylinositol 3,4-bisphostory and catalytic subunits was associated essentially phate, and phosphatidylinositol 3,4,5-trisphosphate with the subplasmalemmal cytoskeleton in both resting (PIP 1) (Kapeller and Cantley, 1994). In many cell and nicotine-stimulated chromaffin cells. Attempts to imtypes, the agonist-stimulated P1 3-kinase utilizes munoprecipitate Pl 3-kinase with anti-phosphotyrosine predominantly phosphatidylinositol 4,5-bisphosphate antibodies failed, suggesting that the activity of P1 3ki-(PIP2) as substrate, and the various 3-phosphorylated nase was not modulated by tyrosine phosphorylation inositol lipids are believed to arise from hydrolysis of and/or physical interaction with SH2-containing proteins newly generated PIP3 (Stephens et al., 1991; Carter et in stimulated chromaffin cells. LY294002 [2-(4-morpholia!., 1994). nyl)-8-phenyl-4H-1-benzopyran-4-one], a potent inhibiAmong the molecular factors underlying constitutor of P1 3-kinase, produced a dose-dependent inhibition of catecholamine secretion evoked by various secretative and regulated exocytosis, proteins have received gogues. Furthermore, cytochemical experiments with particular attention, and their primary role in directing rhodamine-labeled phalloidin revealed that LY294002 membrane interaction and fusion is indisputable (Rothblocked the disassembly of cortical actin in chromaffin man, 1994; Sudhof, 1995). Several lines of evidence cells stimulated by a depolarizing concentration of potassuggest, however, that lipids, in particular the highly sium. Our results suggest that P1 3-kinase may be one phosphorylated metabolites of phosphatidylinositol, of the important regulatory exocytotic components inalso play a fundamental role in vesicular trafficking volved in the signaling cascade controlling actin (De Camilli et al., 1996). The first indication that rearrangements required for catecholamine secretion.inositol phospholipids might be important for Ca 2~-

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Inhibition of Protein Kinase C-Dependent Noradrenaline Release by Wortmannin in PC12 Cells

Cited by 14 publications

References 0 publications

Phorbol myristate acetate induces neutrophil NADPH-oxidase activity by two separate signal transduction pathways: dependent or independent of phosphatidylinositol 3-kinase

Phorbol myristate acetate induces neutrophil NADPH-oxidase activity by two separate signal transduction pathways: dependent or independent of phosphatidylinositol 3-kinase

Phosphatidylinositol 3-Kinase Suppresses Glucose-Stimulated Insulin Secretion by Affecting Post-Cytosolic [Ca2+] Elevation Signals

Possible Involvement of Phosphatidylinositol 3‐Kinase in Regulated Exocytosis: Studies in Chromaffin Cells with Inhibitor LY294002

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