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J Biol Chem, Vol. 273, Issue 30, 19277-19282, July 24, 1998
From the Although it is well appreciated that arachidonic
acid, a second messenger molecule that is released by ligand-stimulated
phospholipase A2, stimulates a wide range of cell
types, the mechanisms that mediate the actions of arachidonic acid are
still poorly understood. We now report that arachidonic acid stimulated
the appearance of dual-phosphorylated (active) p38 mitogen-activated
protein kinase as detected by Western blotting in HeLa cells, HL60
cells, human neutrophils, and human umbilical vein endothelial cells but not Jurkat cells. An increase in p38 kinase activity caused by
arachidonic acid was also observed. Further studies with neutrophils show that the stimulation of p38 dual phosphorylation by arachidonic acid was transient, peaking at 5 min, and was concentration-dependent. The effect of arachidonic acid was not affected by either
nordihydroguaiaretic acid, an inhibitor of the 5-, 12-, and
15-lipoxygenases or by indomethacin, an inhibitor of cyclooxygenase.
Arachidonic acid also stimulated the phosphorylation and/or activity of
the extracellular signal-regulated protein kinase and of c-jun
N-terminal kinase in a cell-type-specific manner. An examination of the
mechanisms through which arachidonic acid stimulated the
phosphorylation/activity of p38 and extracellular signal-regulated
protein kinase in neutrophils revealed an involvement of protein kinase
C. Thus, arachidonic acid stimulated the translocation of protein
kinase C
Stimulation of p38 Phosphorylation and Activity by Arachidonic
Acid in HeLa Cells, HL60 Promyelocytic Leukemic Cells, and Human
Neutrophils
EVIDENCE FOR CELL TYPE-SPECIFIC ACTIVATION OF MITOGEN-ACTIVATED
PROTEIN KINASES
,
,
,
,
, and
Department of Immunopathology, Women's and
Children's Hospital, North Adelaide, South Australia 5006 and
¶ School of Biological Sciences, Flinders University of South
Australia, Bedford Park, South Australia 5042, Australia and
Department of Pharmacology, University of North Carolina,
Chapel Hill, North Carolina 27599
,
I, and
II to a particulate fraction, and the
effects of arachidonic acid on mitogen-activated protein kinase
phosphorylation/activity were partially inhibited by GF109203X, an
inhibitor of protein kinase C. This study is the first to demonstrate
that a polyunsaturated fatty acid causes the dual phosphorylation and
activation of p38.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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