Welsh N
Department of Medical Cell Biology, Uppsala, Sweden.
Biosci Rep. 1994 Feb;14(1):43-50. doi: 10.1007/BF01901637.
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.
本研究的目的是探讨蛋白磷酸化在白细胞介素 -1β（IL -1β）诱导的胰岛素生成细胞信号转导中的假定作用。为此，将胰岛素生成的RINm -5F细胞暴露于IL -1β 7小时，同时添加或不添加蛋白激酶和磷酸酶的不同激动剂和拮抗剂，随后测定亚硝酸盐的生成。先前已经表明，IL -1β会刺激此类细胞中亚硝酸盐的生成。发现乙二胺四乙酸（EDTA）、佛波醇-12-十四酸酯-13-乙酸酯（TPA）和星形孢菌素不影响IL -1β诱导的亚硝酸盐生成。然而，酪氨酸激酶拮抗剂 tyrphostin起抑制作用，而原钒酸钠、冈田酸和环孢菌素A，所有这些蛋白磷酸酶抑制剂，都增强了IL -1β诱导的亚硝酸盐释放到培养基中。酪氨酸激酶拮抗剂染料木黄酮在低浓度下起增强作用，在高浓度下起抑制作用IL -1β的作用。结论是，由蛋白激酶或磷酸酶介导的酪氨酸和丝氨酸/苏氨酸残基上的蛋白磷酸化事件，可能介导或拮抗IL -1诱导的胰岛素生成细胞中的信号转导。
