Signal transduction pathways for activation of extracellular signal-regulated kinase by arachidonic acid in rat neutrophils.
Phosphorylation of extracellular signal-regulated kinase (ERK) in response to arachidonic acid (AA) was rapid and transient, peaking at 1 min and disappearing after 3 min, and it was accompanied by an increase in ERK activity in rat neutrophils. We examined the upstream regulation of AA-stimulated ERK activation using one of the following signaling pathway inhibitors to pretreat rat cells: the ERK kinase inhibitor U0126 or PD98059, the G(i/o) inhibitor pertussis toxin (PTX), the tyrosine kinase inhibitor genistein, the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin or LY294002, the Ca2+ chelator 1,2-bis(O-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid, or the phospholipase C (PLC) inhibitor U73122. All of these inhibitors attenuated AA-induced ERK activation. Activation of ERK was also effectively attenuated by the cyclooxygenase and lipoxygenase inhibitor BW755C and by the leukotriene biosynthesis inhibitor MK886, but the cyclooxygenase inhibitor indomethacin did not attenuate ERK activation. After exposing cells to three distinct protein kinase C (PKC) inhibitors, we found that Gö6976 significantly attenuated ERK phosphorylation but potentiated ERK activity. Neither Gö6983 nor GF109203X affected AA-induced responses. These data suggest that the lipoxygenase metabolite(s) produced mediates AA-stimulated ERK activation and that this effect is upstream regulated by PT-sensitive G protein, non-receptor tyrosine kinase, PI3K, and PLC/Ca2+ signaling pathways in rat neutrophils.
Chang
L C
LC
Department of Education and Research, Taichung Veterans General Hospital, Taiwan, Republic of China.
Wang
J P
JP
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors; D007211:Indoles / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008301:Maleimides / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D037342:Pertussis Toxin; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin; D002722:Chlorobenzenes
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000730:Androstadienes; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D002070:Butadienes; D002118:Calcium; D002227:Carbazoles; D002614:Chelating Agents; D002867:Chromones; D016861:Cyclooxygenase Inhibitors; D004533:Egtazic Acid; D004791:Enzyme Inhibitors; D004963:Estrenes; D005419:Flavonoids; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D008301:Maleimides; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D009570:Nitriles; D037342:Pertussis Toxin; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011760:Pyrrolidinones; D010738:Type C Phospholipases; D010566:Virulence Factors, Bordetella; D000077191:Wortmannin; C113580:U 0126; C081565:arachidonyltrifluoromethane; C060893:MK-886; D002722:Chlorobenzenes; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C081021:Go 6976; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C070515:bisindolylmaleimide I; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one