Delpire E, Gagnon K B
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Acta Physiol (Oxf). 2006 May-Jun;187(1-2):103-13. doi: 10.1111/j.1748-1716.2006.01565.x.
Reversible phosphorylation by protein kinases is probably one of the most important examples of post-translational modification of ion transport proteins. Ste20-related proline alanine-rich kinase (SPAK) and oxidative stress response kinase (OSR1) are two serine/threonine kinases belonging to the germinal centre-like kinase subfamily VI. Genetic analysis suggests that OSR1 evolved first, with SPAK arising following a gene duplication in vertebrate evolution. SPAK and OSR1 are two recently discovered kinases which have been linked to several key cellular processes, including cell differentiation, cell transformation and proliferation, cytoskeleton rearrangement, and most recently, regulation of ion transporters. Na-K-2Cl cotransporter activity is regulated by phosphorylation. Pharmacological evidence has identified several kinases and phosphatases which alter cotransporter function, however, no direct linkage between these enzymes and the cotransporter has been demonstrated. This article will review some of the physical and physiological properties of SPAK and OSR1, and present new evidence of a direct interaction between the Na-K-Cl cotransporter and the stress kinases.
蛋白激酶介导的可逆磷酸化可能是离子转运蛋白翻译后修饰最重要的例子之一。Ste20相关富含脯氨酸丙氨酸激酶（SPAK）和氧化应激反应激酶（OSR1）是属于生发中心样激酶亚家族VI的两种丝氨酸/苏氨酸激酶。遗传分析表明，OSR1首先进化，SPAK是在脊椎动物进化过程中基因复制后出现的。SPAK和OSR1是最近发现的两种激酶，它们与几个关键的细胞过程有关，包括细胞分化、细胞转化和增殖、细胞骨架重排，以及最近发现的离子转运体的调节。钠-钾-2氯共转运体的活性受磷酸化调节。药理学证据已经确定了几种改变共转运体功能的激酶和磷酸酶，然而，这些酶与共转运体之间尚未证明有直接联系。本文将综述SPAK和OSR1的一些物理和生理特性，并提供钠-钾-氯共转运体与应激激酶之间直接相互作用的新证据。
