Differential regulation of Na,K-ATPase isozymes by protein kinases and arachidonic acid
Differential regulation of Na,K-ATPase isozymes by protein kinases and arachidonic acid
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DOI：
10.1006/abbi.1998.0904
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发表时间：
1998-11-15
影响因子：
3.9
通讯作者：
Mercer, RW
中科院分区：
文献类型：
--
作者：
Blanco, G;Sánchez, G;Mercer, RW
虽然一些研究已经调查了由α 1和β 1亚基组成的Na，K-ATP酶的调节，但几乎没有证据表明细胞内信使影响其他Na泵同工酶。我们研究了不同蛋白激酶和花生四烯酸对Sf-9昆虫细胞中表达的大鼠Na，K-ATP酶同工型的影响。我们的研究结果表明，PKA，PKC和PKG能够差异修改的Na，K-ATP酶同工酶的功能。虽然PKC激活导致所有同工酶的抑制，但PKA激活刺激Na，K-ATP酶α 3 β 1的活性并降低α 1 β 1和α 2 β 1同工酶的活性。相比之下，PKG的激活降低了α 1 β 1和α 3 β 1同工酶的活性，而不改变α 2 β 1的活性。用花生四烯酸处理细胞降低了所有同工酶的活性。由PKA和PKC引起的Na泵同工酶的催化能力的变化通过Na，K-ATP酶的分子活性的变化来反映。PKA和PKC影响Na泵同工酶活性的机制之一是通过α亚基的直接磷酸化。在昆虫细胞中，我们发现α 1、α 2和α 3多肽的PKA和PKC依赖性磷酸化。总之，几种细胞内信使能够调节Na，K-ATP酶同工酶的功能，其中一些以特定的方式。由于Na，K-ATP酶同工酶具有独特的动力学特性，因此这种同工酶特异性调节在使Na泵功能适应每个细胞的需求方面可能是重要的。(C)北京：科学出版社.
While several studies have investigated the regulation of the Na,K-ATPase consisting of the alpha 1 and beta 1 subunits, there is little evidence that intracellular messengers influence the other Na pump isozymes. We studied the effect of different protein kinases and arachidonic acid on the rat Na,K-ATPase isoforms expressed in Sf-9 insect cells. Our results indicate that PKA, PKC, and PKG; are able to differentially modify the function of the Na,K-ATPase isozymes. While PKC activation leads to inhibition of all isozymes, PKA activation stimulates the activity of the Na,K-ATPase alpha 3 beta 1 and decreases that of the alpha 1 beta 1 and alpha 2 beta 1 isozymes. In contrast, activation of PKG diminishes the activity of the alpha 1 beta 1 and alpha 3 beta 1 isozymes, without altering that of alpha 2 beta 1. Treatment of cells with arachidonic acid reduced the activities of all the isozymes. The changes in the catalytic capabilities of the Na pump isozymes elicited by PKA and PKC are reflected by changes in the molecular activity of the Na,K-ATPases. One of the mechanisms by which PKA and PKC affect Na pump isozyme activity is through direct phosphorylation of the alpha subunit. In the insect cells, we found a PKA- and PKC-dependent phosphorylation of the alpha 1, alpha 2 and alpha 3 polypeptides. In conclusion, several intracellular messengers are able to modulate the function of the Na,K-ATPase isozymes and some of them in a specific fashion. Because the Na,K-ATPase isozymes have kinetic properties that are unique, this isozyme-specific regulation may be important in adapting Na pump function to the requirements of each cell. (C) 1998 Academic Press.