Agonist Activated PKCβII Translocation and Modulation of Cardiac Myocyte Contractile Function

Overview

Journal Sci Rep

Specialty Science

Date 2013 Jun 13

PMID 23756828

Citations 4

Authors

Hyosook Hwang

Dustin Robinson

Julie B Rogers

Tamara K Stevenson

Sarah E Lang

Sakthivel Sadayappan

Sharlene M Day

Sivaraj Sivaramakrishnan

Margaret V Westfall

Affiliations

Soon will be listed here.

Abstract

Elevated protein kinase C βII (PKCβII) expression develops during heart failure and yet the role of this isoform in modulating contractile function remains controversial. The present study examines the impact of agonist-induced PKCβII activation on contractile function in adult cardiac myocytes. Diminished contractile function develops in response to low dose phenylephrine (PHE, 100 nM) in controls, while function is preserved in response to PHE in PKCβII-expressing myocytes. PHE also caused PKCβII translocation and a punctate distribution pattern in myocytes expressing this isoform. The preserved contractile function and translocation responses to PHE are blocked by the inhibitor, LY379196 (30 nM) in PKCβII-expressing myocytes. Further analysis showed downstream protein kinase D (PKD) phosphorylation and phosphatase activation are associated with the LY379196-sensitive contractile response. PHE also triggered a complex pattern of end-target phosphorylation in PKCβII-expressing myocytes. These patterns are consistent with bifurcated activation of downstream signaling activity by PKCβII.

Citing Articles

Functional communication between PKC-targeted cardiac troponin I phosphorylation sites.

Lang S, Stevenson T, Schatz T, Biesiadecki B, Westfall M Arch Biochem Biophys. 2017; 627:1-9.

PMID: 28587770 PMC: 5555030. DOI: 10.1016/j.abb.2017.05.019.

Contribution of Post-translational Phosphorylation to Sarcomere-Linked Cardiomyopathy Phenotypes.

Westfall M Front Physiol. 2016; 7:407.

PMID: 27683560 PMC: 5021686. DOI: 10.3389/fphys.2016.00407.

Electrical and Mechanical Strategies to Enable Cardiac Repair and Regeneration.

Cao H, Kang B, Lee C, Shung K, Hsiai T IEEE Rev Biomed Eng. 2015; 8:114-24.

PMID: 25974948 PMC: 4579120. DOI: 10.1109/RBME.2015.2431681.

Independent modulation of contractile performance by cardiac troponin I Ser43 and Ser45 in the dynamic sarcomere.

Lang S, Schwank J, Stevenson T, Jensen M, Westfall M J Mol Cell Cardiol. 2014; 79:264-74.

PMID: 25481661 PMC: 4301988. DOI: 10.1016/j.yjmcc.2014.11.022.

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