Activation of CFTR Cl(-) channel by tyrphostins via a protein tyrosine kinase-independent pathway in forskolin-stimulated renal epithelial A6 cells.
Activation of CFTR Cl(-) channel by tyrphostins via a protein tyrosine kinase-independent pathway in forskolin-stimulated renal epithelial A6 cells.
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在毛喉素刺激的肾上皮 A6 细胞中，酪氨酸磷酸酶通过蛋白酪氨酸激酶独立途径激活 CFTR Cl(-) 通道。
DOI：
10.1016/s0024-3205(02)01824-6
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发表时间：
2002
期刊：
影响因子：
6.1
通讯作者：
Y. Marunaka
中科院分区：
文献类型：
--
作者：
N. Niisato;K. Nishio;Y. Marunaka
我们研究了酪氨酸蛋白A23(蛋白酪氨酸激酶的抑制剂)和酪蛋白A63(酪氨酸蛋白A23的非活性类似物)对Forsklin激活的囊性纤维化跨膜电导调节因子(−通道)和肾上皮A6细胞分泌−的影响。Tyrphostin A23和A63对CFTRCI-−通道和CI-−分泌无影响。但在Forsklin刺激条件下，Tyrphostin A23和A63通过激活CFTRCI−通道来刺激CI−的分泌。这些结果提示：1)Tyrphostin A23和A63通过非依赖于PTK的结构依赖的机制激活cAMP激活的CFTRCL−通道；2)tyrphostin A23和A63不刺激cAMP激活的CFTRCI−通道。这使我们认为：1)cAMP可能引起酪氨酸蛋白可进入的CFTRCL-−通道的构象变化，2)酪氨酸菌素通过与cAMP修饰的通道结合来刺激cAMP修饰的通道移位到根尖膜上。
We studied effects of tyrphostin A23 (an inhibitor of protein tyrosine kinase; PTK) and tyrphostin A63 (an inactive analog of tyrphostin A23) on forskolin-activated cystic fibrosis transmembrane conductance regulator (CFTR) Cl−channels and Cl−secretion in renal epithelial A6 cells. Tyrphostin A23 and A63 had no effects on the basal CFTR Cl−channel and Cl−secretion. However, under the forskolin-stimulated condition, tyrphostin A23 and A63 stimulated Cl−secretion by activating CFTR Cl−channels. These observations suggest that: 1) tyrphostin A23 and A63 stimulate the cAMP-activated CFTR Cl−channel via a PTK-independent, structure-dependent mechanism, and 2) tyrphostin A23 and A63 do not stimulate the basal CFTR Cl−channel. These lead us to an idea that: 1) cAMP might cause a conformational change of CFTR Cl−channel which is accessible by tyrphostins, and 2) tyrphostins would stimulate translocation of the cAMP-modified channel to the apical membrane by binding to the channel.
影响因子：
19.6
作者：
Howard, M;Jilling, T;Frizzell, RA
通讯作者：
Frizzell, RA