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.