Roles of Rac and p38 kinase in the activation of cytosolic phospholipase A2 in response to PMA.
The roles of Rac and p38 kinase in the activation of cPLA2 (cytosolic PLA2) in Rat-2 fibroblasts were investigated. In the present study, we found that PMA activates cPLA2 by a Rac-p38 kinase-dependent pathway. Consistent with this, Rac, if activated, was shown to stimulate cPLA2 in a p38 kinase-dependent manner. In another experiment to understand the signalling mechanism by which the Rac-p38 kinase cascade mediates cPLA2 activation in response to PMA, we observed that PMA-induced cPLA2 translocation to the perinuclear region is completely inhibited by the expression of Rac1N17 or treatment with SB203580 (inhibitor of p38 kinase), suggesting that Rac-p38 kinase cascade acts in this instance by mediating the translocation of cPLA2. The mediatory role of p38 kinase in cPLA2 activation was further demonstrated after a treatment with anisomycin, a very effective activator of p38 kinase. Consistent with the mediatory role of p38 kinase in stimulating cPLA2, anisomycin induced the translocation and activation of cPLA2 in a p38 kinase-dependent manner.
You
Hye Jin
HJ
Department of Life Science, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, South Korea.
Woo
Chang-Hoon
CH
Choi
Eun-Young
EY
Cho
Sung-Hoon
SH
Yoo
Yung Joon
YJ
Kim
Jae-Hong
JH
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D021381:Protein Transport; D051381:Rats; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D000841:Anisomycin; D048051:p38 Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D020744:rac GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate