Small heat shock protein 20 (Hsp20) facilitates nuclear import of protein kinase D 1 (PKD1) during cardiac hypertrophy

Cell Communication and Signaling

Research

George S Baillie¹  Lauren Wills¹  Yuan Yan Sin¹  Tamara P Martin¹  Susan Currie² 

[1] Institute of Cardiovascular and Medical sciences, CMVLS, University of Glasgow, G128QQ, Glasgow, UK;Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Hamnett building, 161 Cathedral Street, G4 ORE, Glasgow, UK;

关键词: Hsp20;    PKD1;    Cardiac hypertrophy;    Peptide array;   

DOI  :  10.1186/s12964-015-0094-x

 received in 2014-04-28, accepted in 2015-02-13,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundNuclear import of protein kinase D1 (PKD1) is an important event in the transcriptional regulation of cardiac gene reprogramming leading to the hypertrophic growth response, however, little is known about the molecular events that govern this event. We have identified a novel complex between PKD1 and a heat shock protein (Hsp), Hsp20, which has been implicated as cardioprotective. This study aims to characterize the role of the complex in PKD1-mediated myocardial regulatory mechanisms that depend on PKD1 nuclear translocation.ResultsIn mapping the Hsp20 binding sites on PKD1 within its catalytic unit using peptide array analysis, we were able to develop a cell-permeable peptide that disrupts the Hsp20-PKD1 complex. We use this peptide to show that formation of the Hsp20-PKD1 complex is essential for PKD1 nuclear translocation, signaling mechanisms leading to hypertrophy, activation of the fetal gene programme and pathological cardiac remodeling leading to cardiac fibrosis.ConclusionsThese results identify a new signaling complex that is pivotal to pathological remodelling of the heart that could be targeted therapeutically.

【 授权许可】

Unknown   
© Sin et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.