Phosphorylation of phospholemman (FXYD1) by protein kinases A and C modulates distinct Na,K-ATPase isozymes
Phosphorylation of phospholemman (FXYD1) by protein kinases A and C modulates distinct Na,K-ATPase isozymes
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DOI：
10.1074/jbc.m705830200
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发表时间：
2008-01-04
影响因子：
4.8
通讯作者：
Geering, Kaethi
中科院分区：
文献类型：
--
作者：
Bibert, Stephanie;Roy, Sophie;Geering, Kaethi
PXYD是FXYD蛋白家族的一员，主要在心肌和骨骼肌中表达，它能降低Na，K-ATPase的表观K+和Na+亲和力(Crambert，G.，Fuzesi，M.，Garty，H.，Karlish，S.和Geering，K.(2002)Proc)。娜塔莉。阿卡德。SCI。美国A.99,11476 11481)。在这项研究中，我们使用非洲爪哇卵母细胞表达系统来研究蛋白激酶A和C对磷勒曼磷酸化在心脏中存在的不同Na，K-ATPase同工酶调节中的作用。蛋白激酶A的磷酸化对Na，K-ATPaseα1/β1和α2/β1同工酶的最大转运活性和表观K+亲和力没有影响，但增加了它们的表观Na+亲和力，这依赖于磷脂酶Ser(68)的磷酸化。蛋白激酶C对磷脂酶的磷酸化既不影响α1/β1同工酶的最大转运活性，也不影响α1/β1和α2/β1同工酶的K+亲和力。然而，蛋白激酶C的磷酸化增加了α2/β1同工酶的最大Na，K泵电流，增加了它们的周转次数。因此，我们的结果表明，蛋白激酶A的磷酸化对Na，K-ATPaseα1/β和α2/β同工酶具有相似的作用，并增加了它们的表观Na+亲和力，而蛋白激酶C的磷酸化调节了Na，K-ATPaseα2/β的转运活性，但不调节α1/β同工酶的转运活性。磷酸化对Na，K-ATPase同工酶的复杂而独特的调节可能对心脏收缩和兴奋性的有效控制具有重要意义。
Phospholemman (FXYD1), mainly expressed in heart and skeletal muscle, is a member of the FXYD protein family, which has been shown to decrease the apparent K+ and Na+ affinity of Na,K-ATPase (Crambert, G., Fuzesi, M., Garty, H., Karlish, S., and Geering, K. ( 2002) Proc. Natl. Acad. Sci. U. S. A. 99, 11476 11481). In this study, we use the Xenopus oocyte expression system to study the role of phospholemman phosphorylation by protein kinases A and C in the modulation of different Na, K-ATPase isozymes present in the heart. Phosphorylation of phospholemman by protein kinase A has no effect on the maximal transport activity or on the apparent K+ affinity of Na, K-ATPase alpha 1/beta 1 and alpha 2/beta 1 isozymes but increases their apparent Na+ affinity, dependent on phospholemman phosphorylation at Ser(68). Phosphorylation of phospholemman by protein kinase C affects neither the maximal transport activity of alpha 1/beta 1 isozymes nor the K+ affinity of alpha 1/beta 1 and alpha 2/beta 1 isozymes. However, protein kinase C phosphorylation of phospholemman increases the maximal Na, K-pump current of alpha 2/beta 1 isozymes by an increase in their turnover number. Thus, our results indicate that protein kinase A phosphorylation of phospholemman has similar functional effects on Na, K-ATPase alpha 1/beta and alpha 2/beta isozymes and increases their apparent Na+ affinity, whereas protein kinase C phosphorylation of phospholemman modulates the transport activity of Na, K-ATPase alpha 2/beta but not of alpha 1/beta isozymes. The complex and distinct regulation of Na, K-ATPase isozymes by phosphorylation of phospholemman may be important for the efficient control of heart contractility and excitability.