PKCβII modulation of myocyte contractile performance.

Journal of Molecular and Cellular Cardiology
Hyosook HwangMargaret V Westfall

Abstract

Significant up-regulation of the protein kinase Cβ(II) (PKCβ(II)) develops during heart failure and yet divergent functional outcomes are reported in animal models. The goal here is to investigate PKCβ(II) modulation of contractile function and gain insights into downstream targets in adult cardiac myocytes. Increased PKCβ(II) protein expression and phosphorylation developed after gene transfer into adult myocytes while expression remained undetectable in controls. The PKCβ(II) was distributed in a peri-nuclear pattern and this expression resulted in diminished rates and amplitude of shortening and re-lengthening compared to controls and myocytes expressing dominant negative PKCβ(II) (PKCβDN). Similar decreases were observed in the Ca(2+) transient and the Ca(2+) decay rate slowed in response to caffeine in PKCβ(II)-expressing myocytes. Parallel phosphorylation studies indicated PKCβ(II) targets phosphatase activity to reduce phospholamban (PLB) phosphorylation at residue Thr17 (pThr17-PLB). The PKCβ inhibitor, LY379196 (LY) restored pThr17-PLB to control levels. In contrast, myofilament protein phosphorylation was enhanced by PKCβ(II) expression, and individually, LY and the phosphatase inhibitor, calyculin A each failed to bl...Continue Reading

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Citations

Jan 19, 2013·Circulation Research·R John SolaroTomoyoshi Kobayashi
Oct 22, 2013·Drug Design, Development and Therapy·Ashley Siryk-BathgateAnastasios Lymperopoulos
Jun 13, 2013·Scientific Reports·Hyosook HwangMargaret V Westfall
Jan 13, 2016·Proteomics. Clinical Applications·Evelyn H KimMargaret V Westfall
Aug 2, 2019·The Journal of General Physiology·Vani S RavichandranMargaret V Westfall

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