Proteomic studies of PP2A-B56gamma1 phosphatase complexes reveal phosphorylation-regulated partners in cardiac local signaling |
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Authors: | Zhou Xing Wang Mudannayake Malkanthi Green Mariah Gigena Marisa S Wang Guanghui Shen Rong-Fong Rogers Terry B |
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Institution: | Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. |
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Abstract: | Defects of kinase-phosphatase signaling in cardiac myocytes contribute to human heart disease. The activity of one phosphatase, PP2A, is governed by B targeting subunits, including B56gamma1, expressed in heart cells. As the role of PP2A/B56gamma1 on the heart function remains largely unknown, this study sought to identify protein partners through unbiased, affinity purification-based proteomics combined with the functional validation. The results reveal multiple interactors that are localized in strategic cardiac sites 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 adenovirally overexpressed B56gamma1 is found in z-line/t-tubule region and nuclear speckles. Importantly, overexpression of B56gamma1 in cultured myocytes dramatically impairs cell contractility. These results provide a global view of B56gamma1-regulated local signaling and heart function. |
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