Regulation of cardiac Na–Ca exchange activity by selective tyrosine kinase inhibition

Harvey, Robert D.

doi:10.1038/sj.bjp.0706009

Cited by 3 publications

(1 citation statement)

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“…Myriads of studies starting from the late 1930s have unequivocally shown that protein kinases (PKs) are essential for cellular homeostasis not only in the heart but in virtually any tissue of the body ( Cori et al, 1939 ; Rapundalo, 1998 ; Cohen, 2002a ; Harvey, 2004 ; Johnson, 2009 ; Sato et al, 2015 ). We have now gathered a deep understand how PKs work in the context of cardiovascular diseases (CVDs) and consequently it is anticipated that PKs may serve as the pharmacological drug target of the twenty-first century ( Cohen, 2002a , b ; Force et al, 2004 ; Belmonte and Blaxall, 2011 ; Roskoski, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Counteracting Protein Kinase Activity in the Heart: The Multiple Roles of Protein Phosphatases

et al. 2015

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Decades of cardiovascular research have shown that variable and flexible levels of protein phosphorylation are necessary to maintain cardiac function. A delicate balance between phosphorylated and dephosphorylated states of proteins is guaranteed by a complex interplay of protein kinases (PKs) and phosphatases. Serine/threonine phosphatases, in particular members of the protein phosphatase (PP) family govern dephosphorylation of the majority of these cardiac proteins. Recent findings have however shown that PPs do not only dephosphorylate previously phosphorylated proteins as a passive control mechanism but are capable to actively control PK activity via different direct and indirect signaling pathways. These control mechanisms can take place on (epi-)genetic, (post-)transcriptional, and (post-)translational levels. In addition PPs themselves are targets of a plethora of proteinaceous interaction partner regulating their endogenous activity, thus adding another level of complexity and feedback control toward this system. Finally, novel approaches are underway to achieve spatiotemporal pharmacologic control of PPs which in turn can be used to fine-tune misleaded PK activity in heart disease. Taken together, this review comprehensively summarizes the major aspects of PP-mediated PK regulation and discusses the subsequent consequences of deregulated PP activity for cardiovascular diseases in depth.

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Section: Introductionmentioning

confidence: 99%

Counteracting Protein Kinase Activity in the Heart: The Multiple Roles of Protein Phosphatases

et al. 2015

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Purification, modeling and structural insights of calmodulin-binding receptor like cytoplasmic kinase 2 from Oroxylum Indicum

Ali

Amir

Hassan

et al. 2019

International Journal of Biological Macromolecules

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Roles and regulation of protein phosphatase 2A (PP2A) in the heart

Lubbers

Mohler

2016

Journal of Molecular and Cellular Cardiology

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Reversible protein phosphorylation is central to a variety of cardiac processes including excitation-contraction coupling, Ca2+ handling, cell metabolism, myofilament regulation, and cell-cell communication. While kinase pathways linked with elevated adrenergic signaling have been a major focus for the cardiovascular field over the past half century, new findings support the critical role of protein phosphatases in both health and disease. Protein phosphatase 2A (PP2A) is a central cardiac phosphatase that regulates diverse myocyte functions through a host of target molecules. Notably, multiple mechanisms have evolved to dynamically tune PP2A function, including modulation of the composition, phosphorylation, methylation, and localization of PP2A holoenzyme populations. Further, aberrations in this regulation of PP2A function may contribute to cardiac pathophysiology. In summary, PP2A is a critical regulatory molecule in both health and disease, with a myriad of targets in heart. Based on their unique structure, localization, and regulatory properties, PP2A subunits represent exciting therapeutic targets to modulate altered adrenergic signaling in cardiovascular disease.

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Regulation of cardiac Na–Ca exchange activity by selective tyrosine kinase inhibition

Abstract: British Journal of Pharmacology (2004) 143, 929–930. doi:10.1038/sj.bjp.0706009

Cited by 3 publications

References 5 publications

Counteracting Protein Kinase Activity in the Heart: The Multiple Roles of Protein Phosphatases

Counteracting Protein Kinase Activity in the Heart: The Multiple Roles of Protein Phosphatases

Purification, modeling and structural insights of calmodulin-binding receptor like cytoplasmic kinase 2 from Oroxylum Indicum

Roles and regulation of protein phosphatase 2A (PP2A) in the heart

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