Targeting of Protein Phosphatases PP2A and PP2B to the C-Terminus of the L-Type Calcium Channel Cav1.2

Hui Xu Kenneth S. Ginsburg Duane D. Hall Maike Zimmermann Ivar S. Stein Mingxu Zhang Samvit Tandan Joseph A. Hill Mary C. Horne Donald Bers and Johannes W. Hell

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Targeting of Protein Phosphatases PP2A and PP2B to the C-Terminus of the L-Type Calcium Channel Cav1.2

机译：蛋白质磷酸酶PP2A和PP2B靶向L型钙通道Cav1.2的C末端

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The L-type Ca2þ channel Cav1.2 forms macromolecular signaling complexes that comprise the β2nadrenergic receptor, trimeric Gs protein, adenylyl cyclase, and cAMP-dependent protein kinase (PKA) fornefficient signaling in heart and brain. The protein phosphatases PP2A and PP2B are part of this complex.nPP2A counteracts increase in Cav1.2 channel activity by PKA and other protein kinases, whereas PP2B canneither augment or decrease Cav1.2 currents in cardiomyocytes depending on the precise experimentalnconditions. We found that PP2A binds to two regions in the C-terminus of the central, pore-forming R1nsubunit of Cav1.2: one region spans residues 1795-1818 and the other residues 1965-1971. PP2B bindsnimmediately downstream of residue 1971. Injection of a peptide that contained residues 1965-1971 andndisplaced PP2A but not PP2B fromendogenous Cav1.2 increased basal and isoproterenol-stimulated L-type Ca2þncurrents in acutely isolated cardiomyocytes. Together with our biochemical data, these physiological resultsnindicate that anchoring of PP2A at this site of Cav1.2 in the heart negatively regulates cardiac L-type currents,nlikely by counterbalancing basal and stimulated phosphorylation that is mediated by PKA and possibly othernkinases.

机译：L型Ca2 +通道Cav1.2形成大分子信号复合物，该复合物包含β2肾上腺素能受体，三聚体Gs蛋白，腺苷酸环化酶和cAMP依赖性蛋白激酶（PKA），在心脏和大脑中无用。蛋白磷酸酶PP2A和PP2B是该复合物的一部分。nPP2A抵消了PKA和其他蛋白激酶对Cav1.2通道活性的增加，而PP2B不能根据确切的实验条件增加或减少心肌细胞中Cav1.2的电流。我们发现PP2A绑定到Cav1.2的中央，成孔R1n亚基的C末端的两个区域：一个区域跨越残基1795-1818，另一个残基跨越1965-1971。 PP2B在残基1971的下游直接结合。注射含有1965-1971残基且未置换内源性Cav1.2的PP2A但不置换PP2A的肽会增加急性分离的心肌细胞中基础和异丙肾上腺素刺激的L型Ca2 +电流。连同我们的生化数据，这些生理结果表明，将PP2A锚定在心脏中Cav1.2的此位点可能通过平衡由PKA和其他激酶介导的基础和刺激的磷酸化来负调节心脏L型电流。

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《Biochemistry》 |2010年第48期|p.10298-10307|共10页
作者
Hui Xu Kenneth S. Ginsburg Duane D. Hall Maike Zimmermann Ivar S. Stein Mingxu Zhang Samvit Tandan Joseph A. Hill Mary C. Horne Donald Bers and Johannes W. Hell;
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‡Department of Pharmacology, University of Iowa, Iowa City, Iowa 52242-1109, United States,§Department of Pharmacology,University of California, Davis, California 95616-8636, United States,) Department of Pharmacology, Norman Bethune College ofMedical Sciences, JilinUniversity, Changchun, Jilin 130021,China, and ^Department of InternalMedicine (Cardiology),University ofTexas Southwestern Medical Center, Dallas, Texas 75390-8573, United States;

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1. Targeting of Protein Phosphatases PP2A and PP2B to the C-Terminus of the L-Type Calcium Channel Ca(v)1.2 [J] . Xu H, Ginsburg KS, Hall DD, Biochemistry . 2010,第48期

机译：靶向蛋白磷酸酶PP2A和PP2B至L型钙通道Ca（V）1.2的C-末端
2. Competitive and Non-competitive Regulation of Calcium-dependent Inactivation in CaV1.2 L-type Ca2+ Channels by Calmodulin and Ca2+-binding Protein 1 [J] . Shimrit Oz, Adva Benmocha, Yehezkel Sasson, The Journal of biological chemistry . 2013,第18期

机译：钙调培素和Ca2 + - 桥接蛋白1的Cav1.2 L型Ca2 +通道中钙依赖性灭活的竞争和非竞争调节
3. Developmental Control of CaV1.2 L-Type Calcium Channel Splicing by Fox Proteins [J] . Zhen Zhi Tang, Sika Zheng, Julia Nikolic, Molecular and Cellular Biology . 2009,第17期

机译：Fox蛋白的CaV1.2 L型钙通道剪接的发展控制。
4. PLATELET ACTIVATING FACTOR AFFECTSINTRACELLULAR CALCIUM CONCENTRATION BYMODULATING L-TYPE CALCIUM CHANNEL [C] . TOSHIHIKO KAK International Congress on Electrocardiology . 2005

机译：血小板激活因子血小杂化钙浓度逐调钙型钙通道
5. The Functional and Clinical Phenotypes Caused by Perturbations in CACNA1C-Encoded Cav1.2 L-Type Calcium Channel and the Cav1.2 Interacting Protein, Calmodulin, in the Human Heart. [D] . Boczek, Nicole Joy. 2015

机译：在人心脏中，CACNA1C编码的Cav1.2 L型钙通道和Cav1.2相互作用蛋白Calmodulin扰动引起的功能和临床表型。
6. Targeting of Protein Phosphatases PP2A and PP2B to the C-terminus of the L-type Calcium Channel Cav1.2 [O] . Hui Xu, Kenneth S. Ginsburg, Duane D. Hall, -1

机译：蛋白磷酸酶pp2a和pp2B靶向于L型钙通道Cav1.2的C末端
7. Targeting of Protein Phosphatases PP2A and PP2B to the C Terminus of L-Type Calcium Channel CaV1.2 [O] . Xu Hui, Ginsburg Kenneth, Hall Duane, 2011

机译：将蛋白磷酸酶PP2A和PP2B靶向L型钙通道CaV1.2的C末端

Targeting of Protein Phosphatases PP2A and PP2B to the C-Terminus of the L-Type Calcium Channel Cav1.2

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