A role of p44/42 mitogen‐activated protein kinases in formylpeptide receptor‐mediated phospholipase D activity and oxidant production

  title={A role of p44/42 mitogen‐activated protein kinases in formylpeptide receptor‐mediated phospholipase D activity and oxidant production},
  author={Sylvain Paruch and Jamel El-Benna and Bahia Djerdjouri and Stefano Marullo and Axel Périanin},
  journal={The FASEB Journal},
Phosphatidylcholine‐specific phospholipase D (PLD) is a major cellular source of phosphatidic acid and choline, which regulate various physiopathological processes. PLD activation mediated by chemoattractants involves protein phosphorylation. This study provides pharmacological and biochemical evidence of a major role of p44/42 MAP kinases (ERK1/2) in PLD activation induced by the chemotactic peptide N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP). ERK1/2 inhibition by the MEK1/2 antagonist… 

Protein Kinase B (AKT) Mediates Phospholipase D Activation via ERK1/2 and Promotes Respiratory Burst Parameters in Formylpeptide-stimulated Neutrophil-like HL-60 Cells*

It is shown here that protein kinase B (AKT) is a novel major signaling effector of PLD activity induced by the formylpeptide f-Met-Leu-Phe (fMLP) in human neutrophil-like HL-60 cells (dHL- 60 cells) and forms a complex induced by fMLP, which can be prevented by AKTib1/2.

CCR5 signaling through phospholipase D involves p44/42 MAP‐kinases and promotes HIV‐1 LTR‐directed gene expression

PLD is activated downstream of ERK1/2 upon CCR5 activation and plays a major role in promoting HIV‐1 LTR transactivation and virus replication' which may open novel perspectives to anti‐HIV‐1 strategies.

Gi-Dependent Cell Signaling Responses of the Human P2Y14 Receptor in Model Cell Systems

Results illustrate that the human P2y14-R signals through Gi to inhibit adenylyl cyclase, and P2Y14- R activation also leads to ERK1/2 activation.

Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways Published, JLR Papers in Press, July 3, 2007.

A working model is proposed for S1P in which stimulation of the PI3K/PKB and MEK/ERK pathways leads to the stimulation of PLD and aldosterone secretion.

Phospholipase D1 Plays a Key Role in TNF-α Signaling1

The critical role of PLD1 in the intracellular signaling cascades initiated by TNF-α and its functional role for coordinating the signals to inflammatory responses is demonstrated.

Intracellular Signaling Pathways Regulating Hepatic Apolipoprotein B100 Production: Roles of Mitogen-activated Protein Kinases (MAPKs) and Inhibitor of NFkappaB Kinase (IKK)-NFkappaB

The results suggest that among the MAPK cascades, the MEK-ERK pathway is crucial in regulating apoBlipoprotein assembly, possibly by modulating lipid availability to newly-synthesized apoB.

fMLP induces Hsp27 expression, attenuates NF-kappaB activation, and confers intestinal epithelial cell protection.

Sustained expression of cytoprotective intestinal epithelial heat shock proteins (Hsps), particularly Hsp27, depends on stimuli derived from bacterial flora. In this study, we examined the role of



Essential Role for Phospholipase D2 Activation Downstream of ERK MAP Kinase in Nerve Growth Factor-stimulated Neurite Outgrowth from PC12 Cells*

It is shown that phospholipase D2 (PLD2), which generates the pleiotropic signaling lipid phosphatidic acid (PA), links ERK activation to neurite outgrowth in nerve growth factor (NGF)-stimulated PC12 cells, and functions as a downstream signaling effector of ERK in the NGF signaling pathway.

Phospholipase D2 functions as a downstream signaling molecule of MAP kinase pathway in L1‐stimulated neurite outgrowth of cerebellar granule neurons

Results provide evidence that PLD2 functions as a downstream signaling molecule of ERK to mediate the L1‐dependent neurite outgrowth of CGNs, a mechanism that may be related to alcohol‐related neurodevelopmental disorders.

Phospholipase D Is Required in the Signaling Pathway Leading to p38 MAPK Activation in Neutrophil-like HL-60 Cells, Stimulated by N-Formyl-methionyl-leucyl-phenylalanine*

A role for human PLD1 in fMLP-induced p38 activation in neutrophil-like HL-60 cells is supported and activation of phospholipase D (PLD) was required for activation of p38 but not p44/p42.

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*

Evidence is reported that links the activation of PLD by insulin and the subsequent generation of PA to theactivation of the Raf-1-mitogen-activated protein kinase (MAPK) cascade, and it is found that the recruitment of Raf-2 to the plasma membrane was transient, but Raf- 1 remained bound to endocytic vesicles.

Ras/mitogen-activated protein kinase mediates norepinephrine-induced phospholipase D activation in rabbit aortic smooth muscle cells by a phosphorylation-dependent mechanism.

Results show a novel pathway for activation of PLD that appears to be mediated through Ras/MAP kinase pathway by a mechanism involving phosphorylation, and suggest that NE-stimulated PLD activity is mediated via activation of Ras and MAP kinase in rabbit VSMC.

Role of p38 MAP kinase in diperoxovanadate-induced phospholipase D activation in endothelial cells.

Evidence is provided for p38 MAPK-mediated regulation of PLD in ECs after treatment of ECs with p38MAPK inhibitors and transient transfection with a p38 dominant negative mutant mitigated the PLD activation by DPV but not by phorbol ester.

Contribution of mitogen-activated protein kinase to stimulation of phospholipase D by the chemotactic peptide fMet-Leu-Phe in human neutrophils.

Data provide the first evidence for implication of the ERK cascade in the stimulation of PLD through Gi signaling and indicate that PLD stimulation by fMLP receptors occurs through two pathways, dependent and independent on MAP kinase, the former pathway being linked to superoxide production.

Angiotensin II-Induced Akt Activation through the Epidermal Growth Factor Receptor in Vascular Smooth Muscle Cells Is Mediated by Phospholipid Metabolites Derived by Activation of Phospholipase D

  • Fang LiK. Malik
  • Biology, Chemistry
    Journal of Pharmacology and Experimental Therapeutics
  • 2005
Data indicate that Ang II-stimulated Akt activity is mediated by cPLA2-dependent, p38 MAPK regulated PLD2 activation and EGFR transactivation.

Protein Kinase C ζ Phosphorylates a Subset of Selective Sites of the NADPH Oxidase Component p47phox and Participates in Formyl Peptide-Mediated Neutrophil Respiratory Burst

It is shown that p47phox is a substrate for PKC ζ and participates in the signaling cascade between fMLP receptors and NADPH oxidase activation, and phosphopeptide mapping analysis showed that PKCζ phosphorylated fewer selective sites in comparison to “conventional” PKCs.

Constitutively active mutants of MAP kinase kinase (MEK1) induce growth factor-relaxation and oncogenicity when expressed in fibroblasts.

It is concluded that the downstream elements of the growth factor signalling cascade, MAPKK-MAPK, are both necessary and sufficient to promote growth factor signals and autonomous cell cycling in fibroblasts.