Protein kinase C-independent activation of Raf-1 and mitogen-activated protein kinase by leukotriene B4 in guinea pig eosinophils.
Leukotriene B4 (LTB4) and phorbol 12-myristate 13-acetate (PMA) were found to activate serine/threonine kinase c-Raf-1 (Raf-1) and mitogen-activated protein (MAP) kinase in guinea pig eosinophils. Raf-1 was activated by both compounds in a time- and dose-dependent fashion, and the activation by each paralleled that of MAP kinase. The LTB4 receptor antagonist ONO-4057 prevented the LTB4-induced activation of Raf-1 and MAP kinase, but had no effect on the PMA-induced activation of these kinases. The protein kinase C (PKC) inhibitors, (+/-)1-O-hexadecyl-2-O-methylglycerol (AMG-C16) and bisindolylmaleimide (GF 109203X), suppressed the PMA-induced activation of Raf-1 and MAP kinase, but not the LTB4-induced activation of both kinases. Our findings suggest that the activation of Raf-1 and MAP kinase by LTB4 involves a PKC-independent pathway.
Araki
R
R
Department of Molecular and Cellular Pharmacology, Mie University School of Medicine, Japan.
Komada
T
T
Nakatani
K
K
Naka
M
M
Shima
T
T
Tanaka
T
T
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004804:Eosinophils / Q000201:enzymology*; D005995:Glyceryl Ethers / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D007975:Leukotriene B4 / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D010666:Phenylpropionates / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D017346:Protein Serine-Threonine Kinases / Q000097:blood*; D011518:Proto-Oncogene Proteins / Q000097:blood*; D019908:Proto-Oncogene Proteins c-raf; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D005995:Glyceryl Ethers; D007211:Indoles; D008301:Maleimides; D010666:Phenylpropionates; D011518:Proto-Oncogene Proteins; D018102:Receptors, Leukotriene B4; C059039:1-O-hexadecyl-2-O-methylglycerol; C067523:ONO-LB 457; D007975:Leukotriene B4; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate