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The Role of Protein Kinase A, B, C and D in the Regulation of Cardiomyocyte Contractility (Review). Report I. Pp. 53–61.

Версия для печати

Section: Physiology

UDC

612.172

Authors

Tsirkin Victor Ivanovich, Kazan State Medical University (Kazan, Russia) 

Korotaeva Yuliya Vladimirovna, Postgraduate Student, Natural Geography Faculty, Vyatka State Humanities University (Kirov, Russia)

Abstract

The review focuses on the role of protein kinase A (PKA), protein kinase B (Akt), protein kinase C (PKC) and relatively recently discovered protein kinase D (PKD) in the regulation of the activity of cardiomyocytes and other cells, performed by catecholamines at activation of alpha1-, beta1- and beta2- adrenoceptors (AR). In particular, scientific literature indicates that the activity of cardiomyocyte PKA intensifies during the interaction of catecholamine with beta1- and beta2-AR (at Gs-signaling). This increases permeability of L-type Cachannels, strengthens Ca-pumps of sarcoplasmic reticulum and plasma membrane as well as enhances PKD and Akt activity. Penetrating into the nucleus, PKA regulates the transcription of genes, including neurotrophin genes, brain-derived neurotrophic factor, tyrosine hydroxylase, and c-fos transcription factor. Akt in cardiomyocytes and other cells plays an important role in such processes as glucose transport and metabolism, proliferation, cell migration, apoptosis, transcription, myocardial hypertrophy and brain development. PKC activity in cardiomyocytes intensifies with alpha1-AR activation. It increases permeability of L-type Ca-channels and TRPC-channels for Ca ions, regulates gene transcription, cell cycle and cell growth and activates PKD. In recent years it has been found that PKD is activated by the interaction between catecholamines and alpha1-AR.This kinase is involved in the regulation of myocardial contractility, including by affecting the activity of troponin I and myosin-binding protein C (cMyBP-C), which is addressed in detail in Part 2 of our review. In addition, PKD regulates gene transcription by phosphorylating histone deacetylase 5 (HDAC5) and thereby regulates cardiac hypertrophy and remodelling. PKD also activates NF-kB transcription factor, thus blocking apoptosis. Further, the article shows the role of PKD in heart failure development.

Keywords

protein kinase A, protein kinase B, protein kinase C, protein kinase D, cardiomyocyte, contractility, catecholamines.
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