Regulation of human PLD1 and PLD2 by calcium and protein kinase C

Siddiqi, Abdur Rehman; Srajer, Geraldine; Leslie, Christina C.

doi:10.1016/s0167-4889(00)00049-5

Cited by 60 publications

(46 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6A). Consistent with our results, Siddiqi et al (19) demonstrate that in Sf9 cells, where both PKC␣ and PKC␦ expression are undetectable, PMA barely activated PLD2. However, overexpression of PKC␣, but not PKC␦, significantly enhanced both basal and PMA-stimulated PLD2 activity.…”

Section: Discussionsupporting

confidence: 93%

“…The present results show that PMA stimulates PLD2 activity up to 6-fold when overexpressed in COS-7 cells (Fig. 1), in contrast to a previous report (11) but in agreement with studies in HEK293 and Sf9 cells, where PLD2 also showed large responses to PMA or PKC␣ when overexpressed (19,30).…”

Section: Discussionsupporting

confidence: 93%

“…PLD2 has also been reported to associate with PKC␣ in HEK-293 cells when both proteins were overexpressed, but this association was ligand-independent (30). Siddiqi et al (19) report that when PLD2 and PKC␣ were both overexpressed in Sf9 cells, an association between them was observed and was increased by PMA. It is, therefore, possible that the protein-protein interaction between PLD2 and PKC␣ contributes to the activation of PLD2.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, a lot of activators of PLD2 activity have also been found. These activators include phosphatidylinositol 4,5-bisphosphate (10), unsaturated fatty acid (17), caveolin (18), calcium (19), G M2 activator (20), and adenosine diphosphate ribosylation factor (12). Although the regulation of PLD1 by PKC is universally accepted, it is controversial on whether or not PLD2 is also regulated by PKC.…”

mentioning

confidence: 99%

“…The initial report showed that PLD2 was largely refractory to PKC activation in vitro and in vivo (11). However, recent reports demonstrate that PMA can activate PLD2 in vivo, suggesting the possible regulation of PLD2 activity by PKC (19,21,22). Hence, the role of PKC in PLD2 activation remains to be defined.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Regulation of Phospholipase D2 Activity by Protein Kinase Cα

Chen

Exton

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Regulation of Phospholipase D2 Activity by Protein Kinase Cα

Chen

Exton

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Regulation of Aldosterone Synthesis and Secretion

Bollag

2014

Comprehensive Physiology

150

110

View full text Add to dashboard Cite

Aldosterone is a steroid hormone synthesized in and secreted from the outer layer of the adrenal cortex, the zona glomerulosa. Aldosterone is responsible for regulating sodium homeostasis, thereby helping to control blood volume and blood pressure. Insufficient aldosterone secretion can lead to hypotension and circulatory shock, particularly in infancy. On the other hand, excessive aldosterone levels, or those too high for sodium status, can cause hypertension and exacerbate the effects of high blood pressure on multiple organs, contributing to renal disease, stroke, visual loss, and congestive heart failure. Aldosterone is also thought to directly induce end-organ damage, including in the kidneys and heart. Because of the significance of aldosterone to the physiology and pathophysiology of the cardiovascular system, it is important to understand the regulation of its biosynthesis and secretion from the adrenal cortex. Herein, the mechanisms regulating aldosterone production in zona glomerulosa cells are discussed, with a particular emphasis on signaling pathways involved in the secretory response to the main controllers of aldosterone production, the renin-angiotensin II system, serum potassium levels and adrenocorticotrophic hormone. The signaling pathways involved include phospholipase C-mediated phosphoinositide hydrolysis, inositol 1,4,5-trisphosphate, cytosolic calcium levels, calcium influx pathways, calcium/calmodulin-dependent protein kinases, diacylglycerol, protein kinases C and D, 12-hydroxyeicostetraenoic acid, phospholipase D, mitogen-activated protein kinase pathways, tyrosine kinases, adenylate cyclase, and cAMP-dependent protein kinase. A complete understanding of the signaling events regulating aldosterone biosynthesis may allow the identification of novel targets for therapeutic interventions in hypertension, primary aldosteronism, congestive heart failure, renal disease, and other cardiovascular disorders.

show abstract

Nonoxidative ethanol metabolism in humans—from biomarkers to bioactive lipids

2016

View full text Add to dashboard Cite

Ethanol is a widely used psychoactive drug whose chronic abuse is associated with organ dysfunction and disease. Although the prevalent metabolic fate of ethanol in the human body is oxidation a smaller fraction undergoes nonoxidative metabolism yielding ethyl glucuronide, ethyl sulfate, phosphatidylethanol and fatty acid ethyl esters. Nonoxidative ethanol metabolites persist in tissues and body fluids for much longer than ethanol itself and represent biomarkers for the assessment of ethanol intake in clinical and forensic settings. Of note, the nonoxidative reaction of ethanol with phospholipids and fatty acids yields bioactive compounds that affect cellular signaling pathways and organelle function and may contribute to ethanol toxicity. Thus, despite low quantitative contributions of nonoxidative pathways to overall ethanol metabolism the resultant ethanol metabolites have important biological implications. In this review we summarize the current knowledge about the enzymatic formation of nonoxidative ethanol metabolites in humans and discuss the implications of nonoxidative ethanol metabolites as biomarkers of ethanol intake and mediators of ethanol toxicity. © 2016 IUBMB Life, 68(12):916–923, 2016

show abstract

Regulation of human PLD1 and PLD2 by calcium and protein kinase C

Cited by 60 publications

References 40 publications

Regulation of Phospholipase D2 Activity by Protein Kinase Cα

Regulation of Phospholipase D2 Activity by Protein Kinase Cα

Regulation of Aldosterone Synthesis and Secretion

Nonoxidative ethanol metabolism in humans—from biomarkers to bioactive lipids

Contact Info

Product

Resources

About