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Suppression of IP3-mediated calcium release and apoptosis by Bcl-2 involves the participation of protein phosphatase 1

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Abstract

The involvement and potential interdependence of inositol trisphosphate (IP3) receptors and Bcl-2 in the regulation of Ca2+ signaling is not clear. Here, we have explored the mechanism(s) of how Bcl-2 suppresses the IP3-sensitive Ca2+ release in MCF-7 cells focusing on the possible role of protein phosphatase 1 (PP1). We found that through influences on protein–protein interaction, Bcl-2 may alter the balance between the effects of phosphatase (PP1) and kinase (PKA) on the IP3 R1 signaling complex. Using various experimental approaches including phosphatase inhibition and RNAi, we show that Bcl-2 by competing with IP3R1 for the binding of PP1 can reduce the IP3-mediated calcium signal and protect cells from mitochondrial dysfunction and cell death.

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Abbreviations

IP3:

inositol 1,4,5-trisphosphate

IP3R:

IP3 receptor

Tg:

Thapsigargin

ER:

endoplasmic reticulum

PP1:

protein phosphatase 1

PKA:

protein kinase A

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Acknowledgments

This work was supported by National Institutes of Health (HL-39481, to T.H.K), and CIHR grant FRN 12517 (to DWA). DWA holds the Canada Research Chair in Membrane Biogenesis.

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Authors and Affiliations

  1. Department of Pathology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI, 48201, USA

    Liping Xu, Dejuan Kong, Liping Zhu & Tuan H. Kuo

  2. Department of Biochemistry, McMaster University, West Hamilton, Ontario, L8N 3Z5, Canada

    Weijia Zhu & David W Andrews

  3. Department of Pathology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI, 48201, USA

    Tuan H. Kuo

Authors
  1. Liping Xu
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  2. Dejuan Kong
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  3. Liping Zhu
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  4. Weijia Zhu
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  5. David W Andrews
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  6. Tuan H. Kuo
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Correspondence to Tuan H. Kuo.

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Liping Xu, Dejuan Kong - Equal contribution by these authors

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Xu, L., Kong, D., Zhu, L. et al. Suppression of IP3-mediated calcium release and apoptosis by Bcl-2 involves the participation of protein phosphatase 1. Mol Cell Biochem 295, 153–165 (2007). https://doi.org/10.1007/s11010-006-9285-5

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  • DOI: https://doi.org/10.1007/s11010-006-9285-5

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