Protein kinase C activation enhances cAMP accumulation in Swiss 3T3 cells: inhibition by pertussis toxin.
Protein kinase C activation enhances cAMP accumulation in Swiss 3T3 cells: inhibition by pertussis toxin.
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DOI：
10.1073/pnas.84.8.2282
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发表时间：
1987-04
影响因子：
11.1
通讯作者：
E. Rozengurt;M. Murray;I. Zachary;M. Collins
中科院分区：
文献类型：
--
作者：
E. Rozengurt;M. Murray;I. Zachary;M. Collins
在存在福斯可林或霍乱毒素的情况下，添加phorbol 12,13-二丁酸酯（PBt2）可引起Swiss 3T3细胞中cAMP的显著（6- 8倍）和快速积累。PBt2的作用是由蛋白激酶C介导的，因为合成的二酰基甘油1-油基-2乙酰甘油代替PBt2促进cAMP的积累，因为PBt2或1-油基-2乙酰甘油的增强作用被蛋白激酶C的下调所阻止。加压素激活蛋白激酶C，但不直接影响3T3细胞中的腺苷酸环化酶，在霍乱毒素或福斯可林处理的细胞中也促进cAMP的积累。这种作用被蛋白激酶c的下调所消除。百日咳毒素以浓度和时间依赖的方式阻断了PBt2的增强作用。百日咳毒素既不能阻止PBt2激活蛋白激酶C，也不能阻止PBt2引发的其他生物反应。这里提出的结果表明百日咳毒素底物的一个不寻常的功能-即偶联蛋白激酶C激活到cAMP的产生。
Addition of phorbol 12,13-dibutyrate (PBt2) in the presence of forskolin or cholera toxin caused marked (6- to 8-fold) and rapid accumulation of cAMP in Swiss 3T3 cells. The effect of PBt2 is mediated by protein kinase C because the synthetic diacylglycerol 1-oleoyl-2 acetylglycerol substitutes for PBt2 in enhancing cAMP accumulation and because the enhancing effect of either PBt2 or 1-oleoyl-2-acetylglycerol was prevented by down-regulation of protein kinase C. Vasopressin, which activates protein kinase C but does not directly affect adenylate cyclase in 3T3 cells, also enhanced cAMP accumulation in cells treated with cholera toxin or forskolin. This effect was abolished by down-regulation of protein kinase C. Treatment with pertussis toxin blocked the enhancing effect of PBt2 in a concentration- and time-dependent manner. Pertussis toxin neither prevented protein kinase C activation by PBt2 nor other biologic responses elicited by PBt2. The results presented here suggest an unusual function for a pertussis toxin substrate--namely, coupling protein kinase C activation to cAMP production.