Type II protein kinase A regulates CFTR in airway, pancreatic, and intestinal cells.
Type II protein kinase A regulates CFTR in airway, pancreatic, and intestinal cells.
复制标题
II 型蛋白激酶 A 调节气道、胰腺和肠道细胞中的 CFTR。
DOI：
10.1152/ajpcell.1998.274.3.c819
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Drumm,ML
中科院分区：
文献类型：
--
作者：
Steagall,WK;Kelley,TJ;Marsick,RJ;Drumm,ML
用能够选择性激活I型或II型蛋白激酶A（PKA）的腺苷3′，5 ′-环一磷酸类似物测定了负责囊性纤维化跨膜传导调节因子（CFTR）激活的PKA类型。II型选择性对刺激气道，胰腺和结肠上皮细胞中的氯离子流出; I型选择性对仅刺激气道细胞中的钙依赖性流出。II型选择性类似物激活CFTR介导的电流比I型选择性类似物更大的增加。可溶性PKA活性的测量表明I型和II型选择性类似物刺激的水平相似，产生了关于PKA活性和产生的电流的明显矛盾。此外，在I型选择性类似物后加入毛喉素导致电流增加;在II型选择性类似物后几乎没有增加。类似物刺激的不溶性PKA活性的测量解决了这个矛盾。II型选择性类似物刺激三倍多的不溶性PKA活性的I型选择性对，表明细胞隔室中的PKA的差异激活是重要的CFTR调节。
The type of protein kinase A (PKA) responsible for cystic fibrosis transmembrane conductance regulator (CFTR) activation was determined with adenosine 3′,5′-cyclic monophosphate analogs capable of selectively activating type I or type II PKA. The type II-selective pair stimulated chloride efflux in airway, pancreatic, and colonic epithelial cells; the type I-selective pair only stimulated a calcium-dependent efflux in airway cells. The type II-selective analogs activated larger increases in CFTR-mediated current than did the type I-selective analogs. Measurement of soluble PKA activity demonstrated similar levels stimulated by type I- and type II-selective analogs, creating an apparent paradox regarding PKA activity and current generated. Also, addition of forskolin after the type I-selective analogs resulted in an increase in current; little increase was seen after the type II-selective analogs. Measurement of insoluble PKA activity stimulated by the analogs resolved this paradox. Type II-selective analogs stimulated three times as much insoluble PKA activity as the type I-selective pair, indicating that differential activation of PKA in cellular compartments is important in CFTR regulation.