A mitogen-activated protein kinase independent pathway involved in the phosphorylation and activation of cytosolic phospholipase A2 in human neutrophils stimulated with tumor necrosis factor-alpha.
Although tumor necrosis factor (TNF)-alpha stimulation of human neutrophils does not result in a significant release of arachidonic acid, it primes the cell for arachidonic acid release when cells are further stimulated by agents that induce an intracellular calcium increase. We demonstrate that TNF-alpha stimulation of neutrophils induces the phosphorylation of cytosolic phospholipase A2 (cPLA2) and also increases its activity. These results indicate that although TNF-alpha, by itself, does not cause the release of arachidonic acid in intact cells, it increases the phosphorylation and activation of the enzyme cPLA2. Since we recently found that TNF-alpha stimulation of neutrophils does not increase the tyrosine phosphorylation or activation of the p42erk2 and p44erk1 mitogen-activated protein kinases (MAPKs), the present studies demonstrate the involvement of a MAPK independent pathway in the phosphorylation and activation of cPLA2.
Waterman
W H
WH
Department of Physiology, University of Connecticut Health Center, Farmington 06030, USA.
Sha'afi
R I
RI
D016718:Arachidonic Acid / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D011494:Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2