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Examination of the signal transduction pathways leading to activation of extracellular signal‐regulated kinase by formyl‐methionyl‐leucyl‐phenylalanine in rat neutrophils
Author(s) -
Chang Ling-Chu,
Wang Jih-Pyang
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00717-6
Subject(s) - wortmannin , mapk/erk pathway , protein kinase c , signal transduction , kinase , chemistry , microbiology and biotechnology , phospholipase c , calphostin c , ly294002 , biochemistry , phosphorylation , tyrosine phosphorylation , phosphatidylinositol , biology
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 Ca 2+ chelator BAPTA attenuated ERK activation. These results indicate that G i/o protein, tyrosine kinase, PI3K, PKC, and PLC/Ca 2+ , but not arachidonate metabolites, act upstream of fMLP‐stimulated ERK activation.