Function and regulation of phosphatase 1 in healthy and diseased heart

Klapproth, Erik; Kämmerer, Susanne; El‐Armouche, Ali

doi:10.1016/j.cellsig.2021.110203

Cited by 9 publications

(12 citation statements)

References 141 publications

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“…The phosphorylation of MLC2 is mainly regulated by two kinases, MLCK and ROCK ( 12 , 21 ), and it can be caused by a decrease in protein phosphatase activity ( 22 ). Therefore, we sought to further verify which kinase or phosphatase is primarily involved in the phosphorylation of MLC2 induced by BDNF/TrkB.…”

Section: Resultsmentioning

confidence: 99%

Brain-derived neurotrophic factor regulates LYN kinase–mediated myosin light chain kinase activation to modulate nonmuscle myosin II activity in hippocampal neurons

Yuan

Wang

et al. 2022

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 99%

Brain-derived neurotrophic factor regulates LYN kinase–mediated myosin light chain kinase activation to modulate nonmuscle myosin II activity in hippocampal neurons

Yuan

Wang

et al. 2022

Journal of Biological Chemistry

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“…The fact that different phosphatases associate with individual signalosomes provides further complexity to the regulation of cAMP signals by enabling additional local variation in the signal dynamics. In the heart, protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) catalyse between 70% and 90% of all dephosphorylation events [ 91 ], although protein phosphatase 2B (PP2B) (calcineurin, CaN) also contributes [ 92 ]. The number of phosphatases is significantly smaller than the number of targets they dephosphorylate and substrate specificity primarily relies on the role of regulatory subunit, which also dictate their subcellular localization [ 93 ].…”

Section: Phosphatasesmentioning

confidence: 99%

Compartmentalized cAMP signalling and control of cardiac rhythm

Tomek

Zaccolo

2023

Phil. Trans. R. Soc. B

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In the last 30 years, the field of cyclic adenosine 3′,5′-monophosphate (cAMP) signalling has witnessed a transformative development with the realization that cAMP is compartmentalized and that spatial regulation of cAMP is critical for faithful signal propagation and hormonal specificity. This recognition has changed our understanding of cAMP signalling from the canonical model, where a linear pathway connects a plasma membrane receptor to intracellular effectors and their targets, to a model where signal transduction occurs within a complex network of alternative branches and where an individual receptor leads to activation of a limited fraction of the network, enabled by local regulation of independent signalling units, resulting in a specific functional outcome. The cardiac myocyte has served as the cell model for many of the original findings leading to this paradigm. In this review, we cover some of the evidence supporting this new perspective and discuss how this model is providing novel mechanistic insight into cardiac myocyte physiology. With a focus on the regulation of cardiac rhythm, we consider how this model can provide an original framework for the identification of disease mechanisms. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.

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“…Inhibitor-2, for example, regulates PP1 in plasticity, not only by inhibiting PP1, but also by positively regulating PP1 function in vivo in memory formation ( Foley et al, 2021 ). Further organ-specific functions of PP1 have been extensively described, such as in the heart ( Klapproth et al, 2022 ), being involved in a wide variety of cellular pathways such as DNA-damage response, cell division and translation ( Connor et al, 2001 ; Saurin, 2018 ; Holder et al, 2019 ; Campos and Clemente-Blanco, 2020 ), glycogen metabolism ( Delibegovic et al, 2003 ; Kelsall et al, 2011 ), and embryonic development ( Ferreira et al, 2019 ).…”

Section: Ser/thr Phosphatases In Congenital Diseasesmentioning

confidence: 99%

The role of serine/threonine phosphatases in human development: Evidence from congenital disorders

Vaneynde

Verbinnen²,

Janssens³

2022

Front. Cell Dev. Biol.

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Reversible protein phosphorylation is a fundamental regulation mechanism in eukaryotic cell and organismal physiology, and in human health and disease. Until recently, and unlike protein kinases, mutations in serine/threonine protein phosphatases (PSP) had not been commonly associated with disorders of human development. Here, we have summarized the current knowledge on congenital diseases caused by mutations, inherited or de novo, in one of 38 human PSP genes, encoding a monomeric phosphatase or a catalytic subunit of a multimeric phosphatase. In addition, we highlight similar pathogenic mutations in genes encoding a specific regulatory subunit of a multimeric PSP. Overall, we describe 19 affected genes, and find that most pathogenic variants are loss-of-function, with just a few examples of gain-of-function alterations. Moreover, despite their widespread tissue expression, the large majority of congenital PSP disorders are characterised by brain-specific abnormalities, suggesting a generalized, major role for PSPs in brain development and function. However, even if the pathogenic mechanisms are relatively well understood for a small number of PSP disorders, this knowledge is still incomplete for most of them, and the further identification of downstream targets and effectors of the affected PSPs is eagerly awaited through studies in appropriate in vitro and in vivo disease models. Such lacking studies could elucidate the exact mechanisms through which these diseases act, and possibly open up new therapeutic avenues.

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Function and regulation of phosphatase 1 in healthy and diseased heart

Cited by 9 publications

References 141 publications

Brain-derived neurotrophic factor regulates LYN kinase–mediated myosin light chain kinase activation to modulate nonmuscle myosin II activity in hippocampal neurons

Brain-derived neurotrophic factor regulates LYN kinase–mediated myosin light chain kinase activation to modulate nonmuscle myosin II activity in hippocampal neurons

Compartmentalized cAMP signalling and control of cardiac rhythm

The role of serine/threonine phosphatases in human development: Evidence from congenital disorders

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