Examination of the signal transduction pathways leading to activation of extracellular signal-regulated kinase by formyl-methionyl-leucyl-phenylalanine in rat neutrophils.
The signaling pathways leading to extracellular signal-regulated kinase (ERK) activation in formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated rat neutrophils were examined. fMLP-stimulated ERK activation based on immunoblot analysis with antibodies against the phosphorylation form of ERK was attenuated by the pretreatment of cells with pertussis toxin but not with a dual cyclo-oxygenase/lipoxygenase inhibitor BW755C. Exposure of cells to the tyrosine kinase inhibitor genistein, phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002, or protein kinase C (PKC) inhibitors Gö6976, Gö6983, and GF109203X inhibited fMLP-stimulated ERK phosphorylation in a concentration-dependent manner. In addition, both the phospholipase C (PLC) inhibitor U73122 and the Ca2+ chelator BAPTA attenuated ERK activation. These results indicate that G(i/o) protein, tyrosine kinase, P13K, PKC, and PLC/Ca2+, but not arachidonate metabolites, act upstream of fMLP-stimulated ERK activation.
Department of Education and Research, Taichung Veterans General Hospital, Taiwan, ROC.
L C
LC
Chang
J P
JP
Wang
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D020929:Mitogen-Activated Protein Kinase Kinases; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D004791:Enzyme Inhibitors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins