PMID- 10413116 OWN - NLM STAT- MEDLINE DCOM- 19990809 LR - 20211203 IS - 0014-5793 (Print) IS - 0014-5793 (Linking) VI - 454 IP - 1-2 DP - 1999 Jul 2 TI - Examination of the signal transduction pathways leading to activation of extracellular signal-regulated kinase by formyl-methionyl-leucyl-phenylalanine in rat neutrophils. PG - 165-8 AB - 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 Go6976, Go6983, 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. FAU - Chang, L C AU - Chang LC AD - Department of Education and Research, Taichung Veterans General Hospital, Taiwan, ROC. FAU - Wang, J P AU - Wang JP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (Enzyme Inhibitors) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - EC 3.1.4.- (Type C Phospholipases) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Animals MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors/pharmacology MH - GTP-Binding Proteins/physiology MH - Mitogen-Activated Protein Kinase Kinases MH - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology MH - Neutrophils/*enzymology MH - Protein Kinase C/antagonists & inhibitors MH - Protein Serine-Threonine Kinases/*metabolism MH - Protein-Tyrosine Kinases/*metabolism MH - Rats MH - *Signal Transduction MH - Type C Phospholipases/metabolism EDAT- 1999/07/21 00:00 MHDA- 1999/07/21 00:01 CRDT- 1999/07/21 00:00 PHST- 1999/07/21 00:00 [pubmed] PHST- 1999/07/21 00:01 [medline] PHST- 1999/07/21 00:00 [entrez] AID - S0014-5793(99)00717-6 [pii] AID - 10.1016/s0014-5793(99)00717-6 [doi] PST - ppublish SO - FEBS Lett. 1999 Jul 2;454(1-2):165-8. doi: 10.1016/s0014-5793(99)00717-6.