Fisone G, Cheng S X, Nairn A C, Czernik A J, Hemmings H C, Höög J O, Bertorello A M, Kaiser R, Bergman T, Jörnvall H
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York 10021.
J Biol Chem. 1994 Mar 25;269(12):9368-73.
Phosphorylation of purified Na+,K(+)-ATPase by cAMP-dependent protein kinase (protein kinase A) decreases the activity of this enzyme. We have now shown, using several experimental approaches, that a highly conserved seryl residue on the catalytic (alpha) subunit of Na+,K(+)-ATPase, corresponding to Ser943 of the rat alpha 1 isoform, is the phosphorylation site for protein kinase A. cDNAs corresponding to wild-type Na+,K(+)-ATPase and Na+,K(+)-ATPase in which Ser943 was mutated to Ala were transfected into COS cells. Treatment of the transfected cells with forskolin plus 3-isobutyl-1-methylxanthine resulted in a decrease in the activity of the wild-type enzyme but not in that of the mutated enzyme. The results suggest that, in intact cells, the activity of the Na+,K(+)-ATPase is regulated in part by signal transduction pathways that use protein kinase A-dependent phosphorylation of the Na+,K(+)-ATPase alpha subunit.
环磷酸腺苷（cAMP）依赖性蛋白激酶（蛋白激酶A）对纯化的钠钾ATP酶进行磷酸化会降低该酶的活性。我们现在已经通过几种实验方法表明，钠钾ATP酶催化（α）亚基上一个高度保守的丝氨酸残基，对应于大鼠α1同工型的Ser943，是蛋白激酶A的磷酸化位点。将对应于野生型钠钾ATP酶和Ser943突变为丙氨酸的钠钾ATP酶的cDNA转染到COS细胞中。用福斯可林加3 - 异丁基 - 1 - 甲基黄嘌呤处理转染细胞，导致野生型酶的活性降低，但突变型酶的活性未降低。结果表明，在完整细胞中，钠钾ATP酶的活性部分受信号转导途径调节，这些途径利用蛋白激酶A对钠钾ATP酶α亚基的依赖性磷酸化。
