Proteomic Studies of PP2A-B561 Phosphatase Complexes Reveal Phosphorylation-Regulated Partners in Cardiac Local Signaling

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• 作者：Xing Wang Zhou ; Malkanthi Mudannayake ; Mariah Green ; Marisa S. Gigena ; Guanghui Wang ; Rong-Fong Shen ; Terry B. Rogers
• 刊名：Journal of Proteome Research
• 出版年：2007
• 出版时间：September 2007
• 年：2007
• 卷：6
• 期：9
• 页码：3433 - 3442
• 全文大小：426K
• 年卷期：v.6,no.9(September 2007)
• ISSN：1535-3907

文摘

Defects of kinase-phosphatase signaling in cardiac myocytes contribute to human heart disease. Theactivity of one phosphatase, PP2A, is governed by B targeting subunits, including B561, expressed inheart cells. As the role of PP2A/B561 on the heart function remains largely unknown, this study soughtto identify protein partners through unbiased, affinity purification-based proteomics combined withthe functional validation. The results reveal multiple interactors that are localized in strategic cardiacsites to participate in Ca²⁺ homeostasis and gene expression, exemplified by the Ca pump, SERCA2a,and the splicing factor ASF/SF2. These results are corroborated by confocal imaging where adenovirallyoverexpressed B561 is found in z-line/t-tubule region and nuclear speckles. Importantly, overexpressionof B561 in cultured myocytes dramatically impairs cell contractility. These results provide a globalview of B561-regulated local signaling and heart function.