PKC and PKN in heart disease

Valeria Marrocco; Julius Bogomolovas; Elisabeth Ehler; Cristobal G Dos Remedios; Jiayu Yu; Chen Gao; Stephan Lange

doi:10.1016/j.yjmcc.2019.01.029

PKC and PKN in heart disease

J Mol Cell Cardiol. 2019 Mar:128:212-226. doi: 10.1016/j.yjmcc.2019.01.029. Epub 2019 Feb 8.

Authors

Valeria Marrocco¹, Julius Bogomolovas², Elisabeth Ehler³, Cristobal G Dos Remedios⁴, Jiayu Yu⁵, Chen Gao⁶, Stephan Lange⁷

Affiliations

¹ Division of Cardiology, School of Medicine, University of California-San Diego, La Jolla, USA.
² Division of Cardiology, School of Medicine, University of California-San Diego, La Jolla, USA; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
³ Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, School of Cardiovascular Medicine and Sciences, British Heart Foundation Research Excellence Centre, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
⁴ Bosch Institute, Department of Anatomy, University of Sydney, Sydney. Australia.
⁵ Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, USA. Electronic address: gaochen0813@ucla.edu.
⁷ Division of Cardiology, School of Medicine, University of California-San Diego, La Jolla, USA; University of Gothenburg, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg, Sweden. Electronic address: slange@ucsd.edu.

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.

Keywords: Cardiomyopathy; Kinase; PKC; PKN; Phosphorylation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Cyclic AMP-Dependent Protein Kinases / genetics
Heart Diseases / enzymology
Heart Diseases / genetics*
Heart Diseases / pathology
Humans
Myocardium / enzymology*
Myocardium / pathology
Protein Kinase C / genetics*
Proto-Oncogene Proteins c-akt / genetics
Signal Transduction / genetics

Substances

protein kinase N
Proto-Oncogene Proteins c-akt
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C

Abstract

Publication types

MeSH terms

Substances

Grants and funding