A role for tyrosine kinase activation in interleukin-1 beta induced nitric oxide production in the insulin producing cell line RINm-5F.
The aim of this investigation was to study the putative role of protein phosphorylation in interleukin-1 beta (IL-1 beta) induced signal transduction in insulin producing cells. For this purpose, insulin producing RINm-5F cells were exposed to IL-1 beta for 7 hours with or without different agonists and antagonists to protein kinases and phosphatases and the production of nitrite was subsequently determined. It has been shown earlier that IL-1 beta will stimulate the production of nitrite in such cells. It was found that EDTA, TPA and staurosporine did not affect IL-1 beta induced nitrite production. However, the tyrosine kinase antagonist tyrphostin inhibited, whereas sodium orthovanadate, okadaic acid and cyclosporin A, all inhibitors of protein phosphatases, potentiated IL-1 beta induced nitrite release to the medium. The tyrosine kinase antagonist genistein potentiated at a low concentration and inhibited at a high concentration the IL-1 beta effect. It is concluded that protein phosphorylation events, mediated either by protein kinases or phosphatases on both tyrosine and serine/threonine residues, may mediate or antagonize IL-1 induced signal transduction in insulin producing cells.
Department of Medical Cell Biology, Uppsala, Sweden.
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Welsh
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002396:Catechols / Q000494:pharmacology; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D004789:Enzyme Activation; D019833:Genistein; D007328:Insulin / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020032:Tyrphostins
D000470:Alkaloids; D002396:Catechols; D007328:Insulin; D007375:Interleukin-1; D007529:Isoflavones; D009570:Nitriles; D020032:Tyrphostins; C060152:tyrphostin 47; D009569:Nitric Oxide; D016572:Cyclosporine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate