Shear Stress Activates Cytosolic Phospholipase A2(cPLA2) and MAP Kinase in Human Endothelial Cells

1996 ◽  
Vol 218 (2) ◽  
pp. 500-504 ◽  
Author(s):  
Michael J. Pearce ◽  
Thomas M. McIntyre ◽  
Stephen M. Prescott ◽  
Guy A. Zimmerman ◽  
Ralph E. Whatley
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Phospholipase A2 ◽  
Map Kinase ◽  
Cytosolic Phospholipase A2 ◽  
Human Endothelial Cells ◽  
Cytosolic Phospholipase

scholarly journals Thrombin produces phosphorylation of cytosolic phospholipase A2 by a mitogen-activated protein kinase kinase-independent mechanism in the human astrocytoma cell line 1321N1

1997 ◽  
Vol 328 (1) ◽  
pp. 263-269 ◽  
Author(s):  
Marita HERNÁNDEZ ◽  
Yolanda BAYÓN ◽  
Mariano SÁNCHEZ CRESPO ◽  
María Luisa NIETO
Keyword(s):  
Phospholipase A2 ◽  
Map Kinase ◽  
Cell Line ◽  
Cytosolic Phospholipase A2 ◽  
Thrombin Receptor ◽  
Primary Sequence ◽  
Jun Kinase ◽  
Cytosolic Phospholipase ◽  
Astrocytoma Cell ◽  
Mitogen Activated Protein

The release of [3H]arachidonic acid was studied in the 1321N1 astrocytoma cell line upon stimulation with thrombin. The effect of thrombin was antagonized by hirudin only when both compounds were added simultaneously, which suggests activation of thrombin receptor. Evidence that the cytosolic phospholipase A2 (cPLA2) takes part in thrombin-induced arachidonate release was provided by the finding that thrombin induced retardation of the mobility of cPLA2 in SDS/polyacrylamide gels, which is a feature of the activation of cPLA2 by mitogen-activated protein (MAP) kinases. Thrombin induced activation of two members of the MAP kinase family whose consensus primary sequence appears in cPLA2, namely p42-MAP kinase and c-Jun kinase. However, the activation of c-Jun kinase preceded the phosphorylation of cPLA2 more clearly than the activation of p42-MAK kinase did. Both cPLA2 and c-Jun kinase activation were not affected by PD-98059, a specific inhibitor of MAP kinase kinases, which indeed completely blocked p42-MAP kinase shift. Heat shock, a well-known activator of c-Jun kinase, also phosphorylated cPLA2 but not p42-MAP kinase. These data indicate the existence in astrocytoma cells of a signalling pathway triggered by thrombin receptor stimulation that activates a kinase cascade acting on the Pro-Leu-Ser-Pro consensus primary sequence, activates cPLA2, and associates the release of arachidonate with nuclear signalling pathways.

scholarly journals Role of cytosolic phospholipase A2 in arachidonic acid release of rat-liver macrophages: regulation by Ca2+ and phosphorylation

1995 ◽  
Vol 311 (1) ◽  
pp. 189-195 ◽  
Author(s):  
P Ambs ◽  
M Baccarini ◽  
E Fitzke ◽  
P Dieter
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Map Kinase ◽  
Rat Liver ◽  
Kinase Inhibitor ◽  
Cytosolic Phospholipase A2 ◽  
Ionophore A23187 ◽  
Liver Macrophages ◽  
Cytosolic Phospholipase ◽  
Stimulation Of

In this study we have verified the existence of a cytosolic phospholipase A2 (cPLA2) in rat-liver macrophages. Stimulation of these cells with phorbol 12-myristate 13-acetate (PMA), zymosan and lipopolysaccharide (LPS), but not with the Ca(2+)-ionophore A23187, leads to phosphorylation of cPLA2 and activation of mitogen-activated protein (MAP) kinase, supporting the hypothesis that MAP kinase is involved in cPLA2 phosphorylation. We show furthermore, that the tyrosine kinase inhibitor genistein prevents the LPS- but not the PMA- or zymosan-induced phosphorylation of cPLA2 and activation of MAP kinase, indicating that tyrosine kinases participate in LPS- but not in PMA- and zymosan-induced cPLA2 phosphorylation and MAP kinase activation. Phosphorylation of cPLA2 does not strongly correlate with stimulation of the arachidonic acid (AA) cascade: (1) A23187, a potent stimulator of AA release, fails to induce cPLA2 phosphorylation; (2) withdrawal of extracellular Ca2+, which inhibits PMA-stimulated AA release (Dieter, Schulze-Specking and Decker (1988) Eur. J. Biochem. 177, 61-67), has no effect on PMA-induced phosphorylation of cPLA2; (3) LPS induces cPLA2 phosphorylation within minutes, whereas increased AA release upon treatment with LPS is detectable for the first time after 4 h; and (4) genistein, which prevents LPS-induced cPLA2 phosphorylation, does not inhibit AA release in response to LPS. From these data we suggest that a rise in intracellular Ca2+, but not phosphorylation of cPLA2, is essential for activation of the AA cascade in rat-liver macrophages.

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