PMID- 10708707 OWN - NLM STAT- MEDLINE DCOM- 20000511 LR - 20191210 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 390 IP - 1-2 DP - 2000 Feb 25 TI - Activation of p38 mitogen-activated protein kinase by formyl-methionyl-leucyl-phenylalanine in rat neutrophils. PG - 61-6 AB - The signaling pathways leading to p38 mitogen-activated protein kinase (MAPK) activation in formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated rat neutrophils were examined. Immunoblot analysis with antibodies against a phosphorylated form of p38 MAPK showed that fMLP-stimulated p38 MAPK activation was dependent on a pertussis toxin-sensitive G protein. Two phosphatidylinositol 3-kinase inhibitors, wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), did not affect the p38 MAPK activation. Phosphorylation of p38 MAPK was concentration dependently attenuated by a tyrosine kinase inhibitor, genistein, and by a Ca(2+)-dependent protein kinase C inhibitor, 13-cyanoethyl-12-methyl-6,7,12,13-tetrahydroindolo[2,3-a]pyrrolo[3 , 4-c]carbazole-7-one (Go6976). However, the protein kinase C inhibitors with a broader spectrum, 2-[1-(3-dimethylaminopropyl)-5-methoxy-1H-indol-3-yl]-3-(1H-indol-3-y l)-maleimide (Go6983) and 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimi de (GF109203X), had no inhibitory effect. fMLP-stimulated p38 MAPK phosphorylation was also reduced in cells pretreated with a phospholipase C inhibitor, 1-[6-((17beta-3-methoxyestra-1,3, 5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U73122), or preloaded with an intracellular Ca(2+) chelator, 1, 2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA). We conclude that phosphorylation of p38 MAPK by fMLP stimulation in rat neutrophils is dependent on G(i/o) protein, nonreceptor tyrosine kinase, phospholipase C/Ca(2+), and probably Ca(2+)-dependent protein kinase C pathways. FAU - Chang, L C AU - Chang LC AD - Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Wang, J P AU - Wang JP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Chelating Agents) RN - 0 (Enzyme Activators) RN - 0 (Enzyme Inhibitors) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 1) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.17 (Camk1 protein, rat) RN - EC 2.7.11.17 (Pnck protein, rat) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.1.4.- (Type C Phospholipases) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Type 1 MH - Calcium-Calmodulin-Dependent Protein Kinases/metabolism MH - Chelating Agents/pharmacology MH - Enzyme Activation/drug effects MH - Enzyme Activators/*pharmacology MH - Enzyme Inhibitors/pharmacology MH - GTP-Binding Proteins/metabolism MH - Immunoblotting MH - *Mitogen-Activated Protein Kinases MH - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology MH - Neutrophils/drug effects/*enzymology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation MH - Protein-Tyrosine Kinases/antagonists & inhibitors MH - Rats MH - Type C Phospholipases/antagonists & inhibitors MH - p38 Mitogen-Activated Protein Kinases EDAT- 2000/03/10 09:00 MHDA- 2000/05/20 09:00 CRDT- 2000/03/10 09:00 PHST- 2000/03/10 09:00 [pubmed] PHST- 2000/05/20 09:00 [medline] PHST- 2000/03/10 09:00 [entrez] AID - S0014-2999(00)00033-9 [pii] AID - 10.1016/s0014-2999(00)00033-9 [doi] PST - ppublish SO - Eur J Pharmacol. 2000 Feb 25;390(1-2):61-6. doi: 10.1016/s0014-2999(00)00033-9.