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机构地区:[1]北京工业大学生命科学与生物工程学院,北京100022 [2]蛋白质组学国家重点实验室北京蛋白质组研究中心军事医学科学院放射与辐射医学研究所,北京102206
出 处:《现代生物医学进展》2011年第15期2996-3000,共5页Progress in Modern Biomedicine
基 金:国家863计划"功能基因组和蛋白质组"重大项目课题"人类肝脏蛋白质组表达谱和修饰谱研究"(2006AA02A308)
摘 要:Na-K-Cl协同转运蛋白是一类膜蛋白,负责转运Na、K、Cl离子进出上皮细胞与非上皮细胞。Na-K-Cl介导的转运过程是电中性的,多数情况下是1Na:1K:2Cl(乌贼轴突中是2Na:1 K:3Cl),其活性被布美他尼(bumetanide)和呋塞米(furosemide)所抑制。迄今为止,Na-K-Cl协同转运蛋白被鉴定出来两个同源异构体:NKCC1和NKCC2。NKCC1存在于多个组织中,含有NKCC1的上皮大多数属于分泌上皮,而且会有Na-K-Cl协同转运蛋白位于基底膜外侧;NKCC2只存在于肾脏,位于上皮细胞致密班的顶膜上。Na-K-Cl协同转运蛋白的调控在不同的细胞和组织中是不同的。Na-K-Cl协同转运蛋白的活性会受激素刺激和细胞体积变化的影响;有些组织中,这种调控作用(尤其是NKCC1亚基)是通过特定的激酶使该转运蛋白自身发生氧化/硝化、磷酸化/去磷酸化来实现的;蛋白过表达在Na-K-Cl协同转运蛋白的激活中也起重要作用。The Na-K-Cl cotransporters are a class of membrane proteins that transport Na, K, and Cl ions into and out of a wide variety of epithelial and nonepithelial cells.The transport process mediated by Na-K-Cl cotransporters is characterized by electrically neutral stoichiometries of 1 Na:l K:2 Cl (for most cells) and 2 Na:l K:3 Cl (in squid axon) and inhibition by the "loop" diuretics bumetanide and furosemide. So far, two distinct Na-K-Cl cotransporter isoforms have been identified, named NKCC1 and NKCC2. The NKCC1 isoform is present in a wide variety of tissues, most epithelia containing NKCCl are secretory epithelia with the Na-K-Cl cotransporter localized to the basolateral membrane; NKCC2 is found only in the kidney, localized to the apical membrane of the epithelial cells of the thick ascending limb. The regulation of Na-K-Cl cotransport is extremely diverse, and varies greatly among different cells and tissues. Na-K-Cl cotransporter activity is affected by a large variety of hormonal stimuli as well as by changes in cell volume; in many tissues this regulation (particularly of the NKCCl isoform) occurs through direct oxidative/nitrosative, phosphorylation/dephosphorylation of the cotransport protein itself through the specific protein kinases. Increased NKCC 1 protein expression was recently shown to contribute to its increased activity.
关 键 词:Na-K-Cl协同转运蛋白 布美他尼 活性调控
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