Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 128, Issue -, Pages 212-226Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2019.01.029
Keywords
PKC; PKN; Kinase; Cardiomyopathy; Phosphorylation
Categories
Funding
- NIH [HL128457, HL107744, 20180199]
- Swedish Hjart-Lungfonden [HL128457, HL107744, 20180199]
- British Heart Foundation [RE/13/2/30182]
- MRC [MR/R017050/1]
- European Commission [656636]
- American Heart Association [17POST33661136]
- Marie Curie Actions (MSCA) [656636] Funding Source: Marie Curie Actions (MSCA)
- Swedish Heart-Lung Foundation [20180199] Funding Source: Swedish Heart-Lung Foundation
- MRC [MR/R017050/1] Funding Source: UKRI
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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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