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Sergienko NM, Donner DG, Delbridge LMD, et al. Protein phosphatase 2A in the healthy and failing heart: New insights and therapeutic opportunities. Cell Signal. 2021;91:110213doi: 10.1016/j.cellsig.2021.110213.
Sergienko, N. M., Donner, D. G., Delbridge, L. M. D., McMullen, J. R., & Weeks, K. L. (2021). Protein phosphatase 2A in the healthy and failing heart: New insights and therapeutic opportunities. Cellular signalling, 91110213. https://doi.org/10.1016/j.cellsig.2021.110213
Sergienko, Nicola M, et al. "Protein phosphatase 2A in the healthy and failing heart: New insights and therapeutic opportunities." Cellular signalling vol. 91 (2021): 110213. doi: https://doi.org/10.1016/j.cellsig.2021.110213
Sergienko NM, Donner DG, Delbridge LMD, McMullen JR, Weeks KL. Protein phosphatase 2A in the healthy and failing heart: New insights and therapeutic opportunities. Cell Signal. 2021 Dec 10;91:110213. doi: 10.1016/j.cellsig.2021.110213. Epub 2021 Dec 10. PMID: 34902541.
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Cell Signal. 2021 Dec 10;91:110213. doi: 10.1016/j.cellsig.2021.110213. Epub 2021 Dec 10.

Protein phosphatase 2A in the healthy and failing heart: New insights and therapeutic opportunities.

Cellular signalling

Nicola M Sergienko, Daniel G Donner, Lea M D Delbridge, Julie R McMullen, Kate L Weeks

Affiliations

  1. Baker Heart and Diabetes Institute, Melbourne VIC 3004, Australia; Central Clinical School, Monash University, Clayton VIC 3800, Australia.
  2. Baker Heart and Diabetes Institute, Melbourne VIC 3004, Australia; Baker Department of Cardiometabolic Health, The University of Melbourne, Parkville VIC 3010, Australia.
  3. Department of Anatomy and Physiology, The University of Melbourne, Parkville VIC 3010, Australia.
  4. Baker Heart and Diabetes Institute, Melbourne VIC 3004, Australia; Baker Department of Cardiometabolic Health, The University of Melbourne, Parkville VIC 3010, Australia; Department of Physiology and Department of Medicine Alfred Hospital, Monash University, Clayton VIC 3800, Australia; Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora VIC 3086, Australia; Department of Diabetes, Central Clinical School, Monash University, Clayton VIC 3800, Australia. Electronic address: [email protected].
  5. Baker Heart and Diabetes Institute, Melbourne VIC 3004, Australia; Department of Anatomy and Physiology, The University of Melbourne, Parkville VIC 3010, Australia; Baker Department of Cardiometabolic Health, The University of Melbourne, Parkville VIC 3010, Australia; Department of Diabetes, Central Clinical School, Monash University, Clayton VIC 3800, Australia. Electronic address: [email protected].

PMID: 34902541 DOI: 10.1016/j.cellsig.2021.110213

Abstract

Protein phosphatases have emerged as critical regulators of phosphoprotein homeostasis in settings of health and disease. Protein phosphatase 2A (PP2A) encompasses a large subfamily of enzymes that remove phosphate groups from serine/threonine residues within phosphoproteins. The heterogeneity in PP2A structure, which arises from the grouping of different catalytic, scaffolding and regulatory subunit isoforms, creates distinct populations of catalytically active enzymes (i.e. holoenzymes) that localise to different parts of the cell. This structural complexity, combined with other regulatory mechanisms, such as interaction of PP2A heterotrimers with accessory proteins and post-translational modification of the catalytic and/or regulatory subunits, enables PP2A holoenzymes to target phosphoprotein substrates in a highly specific manner. In this review, we summarise the roles of PP2A in cardiac physiology and disease. PP2A modulates numerous processes that are vital for heart function including calcium handling, contractility, β-adrenergic signalling, metabolism and transcription. Dysregulation of PP2A has been observed in human cardiac disease settings, including heart failure and atrial fibrillation. Efforts are underway, particularly in the cancer field, to develop therapeutics targeting PP2A activity. The development of small molecule activators of PP2A (SMAPs) and other compounds that selectively target specific PP2A holoenzymes (e.g. PP2A/B56α and PP2A/B56ε) will improve understanding of the function of different PP2A species in the heart, and may lead to the development of therapeutics for normalising aberrant protein phosphorylation in settings of cardiac remodelling and dysfunction.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: Heart failure; Kinases; PP2A; Protein phosphatase 2A; Therapies

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