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Enhanced PKC beta II translocation and PKC beta II-RACK1 interactions in PKC epsilon-induced heart failure: a role
1Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky 40202, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|November 16, 2001
Summary
Protein kinase C epsilon (PKC epsilon) activation leads to cardiac hypertrophy and failure by enhancing PKC beta II signaling through RACK1. This study reveals RACK1 as a key coordinator of these PKC-mediated pathways in the heart.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Protein kinase C beta II (PKC beta II) is implicated in cardiac hypertrophy and failure.
- Receptors for activated C kinase (RACKs) direct PKC signaling, with RACK1 selectively binding PKC beta II.
- Previous work suggested PKC epsilon (PKC epsilon) modulates RACK expression and interactions, potentially influencing cardiac phenotypes.
Purpose of the Study:
- To define the mechanism by which RACK1 participates in PKC beta II-mediated cardiac hypertrophy and failure.
- To investigate the role of PKC epsilon in PKC beta II signaling and RACK1 interactions within the heart.
Main Methods:
- Assessed left ventricular function and myocardial hypertrophy in transgenic mice with high PKC epsilon activity.
- Quantified PKC beta II and RACK1 colocalization and PKC beta II subcellular distribution.
- Examined PKC beta II-RACK1 interactions and RACK1 expression levels.
Main Results:
- High PKC epsilon activity correlated with impaired cardiac function and significant myocardial hypertrophy.
- PKC epsilon activation induced increased colocalization of PKC beta II with RACK1 and redistribution of PKC beta II to the particulate fraction.
- Enhanced PKC beta II activation was linked to increased RACK1 expression and PKC beta II-RACK1 interactions.
Conclusions:
- PKC epsilon activation promotes PKC beta II signaling through a RACK1-dependent mechanism, contributing to cardiac hypertrophy and failure.
- RACK1 acts as a central coordinator for both PKC epsilon and PKC beta II signaling pathways in the heart.
- These findings elucidate a novel signaling axis in the pathogenesis of cardiac hypertrophy and failure.
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