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PKC and PKN in heart disease

Journal article
Authors V. Marrocco
J. Bogomolovas
E. Ehler
C. G. dos Remedios
J. Y. Yu
C. Gao
Stephan Lange
Published in Journal of Molecular and Cellular Cardiology
Volume 128
Pages 212-226
ISSN 0022-2828
Publication year 2019
Published at Wallenberg Laboratory
Pages 212-226
Language en
Links dx.doi.org/10.1016/j.yjmcc.2019.01....
Keywords PKC, PKN, Kinase, Cardiomyopathy, Phosphorylation, protein-kinase-c, cardiac allograft-rejection, ischemia-reperfusion, injury, zipper-like sequences, oxidase subunit-iv, troponin-i, induced, phosphorylation, delta-pkc, pharmacological inhibition, dependent, phosphorylation, Cardiovascular System & Cardiology, Cell Biology
Subject categories Clinical Medicine

Abstract

The protein kinase C (PKC) and closely related protein kinase N (PKN) families of serine/threonine protein kinases play crucial cellular roles. Both kinases belong to the AGC subfamily of protein kinases that also include the CAMP dependent protein kinase (PKA), protein kinase B (PKB/AKT), protein kinase G (PKG) and the ribosomal protein S6 kinase (S6K). Involvement of PKC family members in heart disease has been well documented over the years, as their activity and levels are mis-regulated in several pathological heart conditions, such as ischemia, diabetic cardiomyopathy, as well as hypertrophic or dilated cardiomyopathy. This review focuses on the regulation of PKCs and PKNs in different pathological heart conditions and on the influences that PKC/PKN activation has on several physiological processes. In addition, we discuss mechanisms by which PKCs and the closely related PKNs are activated and turned-off in hearts, how they regulate cardiac specific downstream targets and pathways, and how their inhibition by small molecules is explored as new therapeutic target to treat cardiomyopathies and heart failure.

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