NUCLEOSIDE TRIPHOSPHATES ARE REQUIRED TO OPEN THE CFTR CHLORIDE CHANNEL
NUCLEOSIDE TRIPHOSPHATES ARE REQUIRED TO OPEN THE CFTR CHLORIDE CHANNEL
复制标题
DOI：
10.1016/0092-8674(91)90072-7
复制
发表时间：
1991-11-15
期刊：
影响因子：
64.5
通讯作者：
WELSH, MJ
中科院分区：
文献类型：
--
作者：
ANDERSON, MP;BERGER, HA;WELSH, MJ
CFTR Cl-通道含有两个预测的核苷酸结合结构域（NBD 1和NBD 2）;因此，我们研究了ATP对通道活性的影响。一旦被cAMP依赖性蛋白激酶（PKA）磷酸化，通道需要胞浆ATP打开。激活发生的PKA独立的机制。ATP-γ-S在PKA磷酸化中取代ATP，但不打开通道。几种可水解的核苷酸（ATP > GTP > ITP几乎等于UTP > CTP）可逆地激活磷酸化通道，但不可水解的类似物和无Mg 2+的ATP不激活。CFTR突变体的研究表明，ATP控制通道活性的R结构域独立，并建议ATP的水解NBD 1可能是足够的通道开放。三磷酸核苷调节CFTR的发现开始解释NBD中CF相关突变阻断Cl-通道功能的原因。
The CFTR Cl- channel contains two predicted nucleotide-binding domains (NBD1 and NBD2); therefore, we examined the effect of ATP on channel activity. Once phosphorylated by cAMP-dependent protein kinase (PKA), channels required cytosolic ATP to open. Activation occurred by a PKA-independent mechanism. ATP-gamma-S substituted for ATP in PKA phosphorylation, but it did not open the channel. Several hydrolyzable nucleotides (ATP > GTP > ITP almost-equal-to UTP > CTP) reversibly activated phosphorylated channels, but nonhydrolyzable analogs and Mg2+-free ATP did not. Studies of CFTR mutants indicated that ATP controls channel activity independent of the R domain and suggested that hydrolysis of ATP by NBD1 may be sufficient for channel opening. The finding that nucleoside triphosphates regulate CFTR begins to explain why CF-associated mutations in the NBDs block Cl- channel function.