scholarly journals Role of phospholipase D in the cAMP signal transduction pathway activated during fibroblast contraction of collagen matrices.

1995 ◽  
Vol 130 (5) ◽  
pp. 1197-1205 ◽  
Author(s):  
Y He ◽  
F Grinnell
Keyword(s):  
Signal Transduction ◽  
Arachidonic Acid ◽  
Protein Kinase C ◽  
Phosphatidic Acid ◽  
Phospholipase D ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Collagen Matrices ◽  
Kinase C ◽  
Acid Release

Fibroblast contraction of stressed collagen matrices results in activation of a cAMP signal transduction pathway. This pathway involves influx of extracellular Ca2+ ions and increased production of arachidonic acid. We report that within 5 min after initiating contraction, a burst of phosphatidic acid release was detected. Phospholipase D was implicated in production of phosphatidic acid based on observation of a transphosphatidylation reaction in the presence of ethanol that resulted in formation of phosphatidylethanol at the expense of phosphatidic acid. Activation of phospholipase D required extracellular Ca2+ ions and was regulated by protein kinase C. Ethanol treatment of cells also inhibited by 60-70% contraction-dependent release of arachidonic acid and cAMP but had no effect on increased cAMP synthesis after addition of exogenous arachidonic acid or on phospholipase A2 activity measured in cell extracts. Moreover, other treatments that inhibited the burst of phosphatidic acid release after contraction--chelating extracellular Ca2+ or down-regulating protein kinase C--also blocked contraction activated cyclic AMP signaling. These results were consistent with the idea that phosphatidic acid production occurred upstream of arachidonic acid in the contraction-activated cAMP signaling pathway.

scholarly journals Interleukin 1-β-induced protein kinase C-ζ activation is mimicked by exogenous phospholipase D

1997 ◽  
Vol 321 (2) ◽  
pp. 497-502 ◽  
Author(s):  
Cristina LIMATOLA ◽  
Benedetta BARABINO ◽  
Anna NISTA ◽  
Angela SANTONI
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Phosphatidic Acid ◽  
Phospholipase D ◽  
Biological Effects ◽  
Interleukin 1 ◽  
Signal Transduction Pathways ◽  
Kinase C ◽  
Pkc Ζ

Interleukin 1-α (IL1-α) is a pleiotropic cytokine that stimulates a number of signal transduction pathways in cells, leading to different cellular responses. In this study we investigated the signal transduction pathways activated by IL1-α in two different human cell lines: RD/TE671, a rhabdomyosarcoma, and EJ, a bladder-derived carcinoma. We showed that this cytokine induced the activation of protein kinase C-ζ (PKC-ζ) and the accumulation of a putative physiological PKC-ζ activator, phosphatidic acid [Limatola, Schaap, Moolenaar and van Blitterswijk (1994) Biochem. J. 304, 1001Ő1008]. Exogenously supplied phospholipase D, which generated cellular phosphatidic acid, was able to mimic the cytokine effect, supporting the hypothesis that this lipid second messenger might contribute to cytokine-induced PKC-ζ activation. In addition, we show that IL1-α stimulation of BOSC23 cells, transiently overexpressing PKC-ζ, induced an increase in PKC-ζ autophosphorylation. These results give the first direct evidence that IL1-α can activate this atypical PKC isoform and suggest that this enzyme might be involved in mediating some of the biological effects induced by IL1-α.

scholarly journals Lactosylceramide-enriched glycosphingolipid signaling domain mediates superoxide generation from human neutrophils

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1454-1464 ◽  
Author(s):  
Kazuhisa Iwabuchi ◽  
Isao Nagaoka
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Superoxide Generation ◽  
Kinase C ◽  
Signaling Domain

This study is focused on the functional significance of neutrophil lactosylceramide (LacCer)–enriched microdomains, which are involved in the initiation of a signal transduction pathway leading to superoxide generation. Treatment of neutrophils with anti-LacCer antibody, T5A7 or Huly-m13, induced superoxide generation from the cells, which was blocked by PP1, a Src kinase inhibitor; wortmannin, a phosphatidylinositol-3 kinase inhibitor; SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor; and H7, an inhibitor for protein kinase C. When promyelocytic leukemia HL-60 cells were differentiated into neutrophilic lineage by dimethyl sulfoxide (DMSO) treatment, they acquired superoxide-generating activity but did not respond to anti-LacCer antibodies. Density gradient centrifugation revealed that LacCer and Lyn were recovered in detergent-insoluble membrane (DIM) of neutrophils and DMSO-treated HL-60 cells. However, immunoprecipitation experiments indicated that LacCer was associated with Lyn in neutrophils but not in DMSO-treated HL-60 cells. Interestingly, T5A7 induced the phosphorylation of Lyn in neutrophils but not in DMSO-treated HL-60 cells. Moreover, T5A7 induced the phosphorylation of p38 MAPK in neutrophils. T5A7-induced Lyn phosphorylation in neutrophil DIM fraction was significantly enhanced by cholesterol depletion or sequestration with methyl-β-cyclodextrin or nystatin. Collectively, these data suggest that neutrophils are characterized by the presence of cell surface LacCer-enriched glycosphingolipid signaling domain coupled with Lyn and that the ligand binding to LacCer induces the activation of Lyn, which may be suppressibly regulated by cholesterol, leading to superoxide generation through the phosphatidylinositol-3 kinase–, p38 MAPK–, and protein kinase C–dependent signal transduction pathway.

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