Leukotriene D4-induced activation of protein kinase C in rat basophilic leukemia cells.
We studied the subcellular distribution of protein kinase C (PKC) in the particulate and cytosolic fractions of rat basophilic leukemia (RBL-1) cells treated with leukotriene D4 (LTD4) and compared these results with those of phorbol myristate acetate (PMA). Consistent with the earlier reports, treatment of RBL-1 cells with PMA resulted in a time- and dose-dependent translocation of PKC from cytosolic to the particulate fractions, sustained for at least 10 min. When RBL-1 cells were treated with LTD4, a small, transient decrease in PKC activity in cytosolic fraction was observed within 7.5 s after LTD4 treatment. This was accompanied by a significant increase of PKC in the particulate fraction. However, at 15 and 30 s, both particulate and cytosolic PKC activities were increased with LTD4 treatment. The activation induced by LTD4 was dose- and time-dependent with maximal effects occurring within 30 s, declining at the later time points. Pretreatment of the cells with 2(R)-hydroxy-3(S)-carboxyethylthio-3-[2-(8-phenyloctyl,pheny l]propanoic acid (SK&F 104353), a high affinity specific LTD4 receptor antagonist, and also with staurosporine, a potent inhibitor of PKC, completely inhibited the LTD4-induced activation of PKC both in the particulate and cytosolic fractions. These results suggest that activation of PKC by LTD4 is different from that elicited by PMA. The ability of SK&F 104353 to block LTD4-induced activation of PKC further suggests that stimulation of PKC might be an important intermediate step in the signal transduction mechanism of the LTD4 receptor in RBL-1 cells.
Vegesna
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RV
Department of Molecular Pharmacology, Smith Kline & French Laboratories, King of Prussia, PA 19406-0939.
Mong
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Crooke
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D000818:Animals; D001491:Basophils / Q000201:enzymology; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D007942:Leukemia, Experimental / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism; D013189:SRS-A / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000201:enzymology
D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin; D013189:SRS-A; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate