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Signal transduction pathways for activation of extracellular signal‐regulated kinase by arachidonic acid in rat neutrophils
Author(s) -
Chang LingChu,
Wang JihPyang
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.4.659
Subject(s) - mapk/erk pathway , wortmannin , biology , ly294002 , kinase , protein kinase c , signal transduction , mek inhibitor , microbiology and biotechnology , tyrosine phosphorylation , phosphorylation , arachidonic acid , protein kinase a , protein kinase b , tyrosine kinase , mitogen activated protein kinase kinase , biochemistry , enzyme
Phosphorylation of extracellular signal‐regulated kinase (ERK) inresponse to arachidonic acid (AA) was rapid and transient, peaking at 1min and disappearing after 3 min, and it was accompanied by an increasein ERK activity in rat neutrophils. We examined the upstream regulationof AA‐stimulated ERK activation using one of the following signalingpathway inhibitors to pretreat rat cells: the ERK kinase inhibitorU0126 or PD98059, the G i/o inhibitor pertussis toxin (PTX),the tyrosine kinase inhibitor genistein, the phosphatidylinositol3‐kinase (PI3K) inhibitor wortmannin or LY294002, the Ca 2+ 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‐inducedERK activation. Activation of ERK was also effectively attenuated bythe cyclooxygenase and lipoxygenase inhibitor BW755C and by theleukotriene biosynthesis inhibitor MK886, but the cyclooxygenaseinhibitor indomethacin did not attenuate ERK activation. After exposingcells to three distinct protein kinase C (PKC) inhibitors, we foundthat Gö6976 significantly attenuated ERK phosphorylation butpotentiated ERK activity. Neither Gö6983 nor GF109203Xaffected AA‐induced responses. These data suggest that the lipoxygenasemetabolite(s) produced mediates AA‐stimulated ERK activation and thatthis effect is upstream regulated by PT‐sensitive G protein,nonreceptor tyrosine kinase, PI3K, and PLC/Ca 2+ signalingpathways in rat neutrophils.