Skip Navigation


Cardiovascular Research Advance Access first published online on February 23, 2008
This version [Corrected Proof] published online on March 25, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn052
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
78/3/458    most recent
cvn052v2
cvn052v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Maturana, A. D.
Right arrow Articles by Kuroda, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maturana, A. D.
Right arrow Articles by Kuroda, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Enigma homolog 1 scaffolds protein kinase D1 to regulate the activity of the cardiac L-type voltage-gated calcium channel

Andrés D. Maturana1,2,*, Sébastien Wälchli3, Miki Iwata1, Stephan Ryser4, Johannes Van Lint5, Masahiko Hoshijima6, Werner Schlegel4, Yasuhiro Ikeda7, Katsuyuki Tanizawa1 and Shun'ichi Kuroda1

1 Department of Structural Molecular Biology, Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan
2 Global Edge Institute, Tokyo Institute of Technology, E31, Okayama 2-1-12 Meguro, Tokyo 152-8550, Japan
3 Department of Immunology, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, 0310 Oslo, Norway
4 Fondation pour Recherches Médicales, 1217 Geneva, Switzerland
5 Afdeling Biochemie, Katholieke Universiteit Leuven, Leuven B-3000, Belgium
6 Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0734, USA
7 Department of Medical Bioregulation, Yamaguchi University School of Medicine, 755-8505 Yamaguchi, Japan

* Corresponding author. Tel/fax: +81 459245141. E-mail address: amaturana{at}bio.titech.ac.jp

Aims: In cardiomyocytes, protein kinase D1 (PKD1) plays a central role in the response to stress signals. From a yeast two-hybrid assay, we have identified Enigma Homolog 1 (ENH1) as a new binding partner of PKD1. Since in neurons, ENH1, associated with protein kinase C{varepsilon}, was shown to modulate the activity of N-type calcium channels, and the pore-forming subunit of the cardiac L-type voltage-gated calcium channel, {alpha}1C, possesses a potential phosphorylation site for PKD1, we studied here a possible role of ENH1 and PKD1 in the regulation of the cardiac L-type voltage-gated calcium channel.

Methods and results: PKD1-interacting proteins were searched by yeast two-hybrid screening. In vivo protein interactions in cardiomyocytes isolated from heart ventricles of newborn rats were tested by co-immunoprecipitation. Small interfering RNA and a dominant negative mutant of PKD1 were delivered into cardiomyocytes by use of an adenovirus. Calcium currents were measured by the patch-clamp technique. Both ENH1 and PKD1 interact with {alpha}1C in cardiomyocytes. This interaction is increased upon stimulation. Silencing of ENH1 prevented the binding of PKD1 to {alpha}1C. Moreover, a dominant negative mutant of PKD1 or the silencing of ENH1 inhibited the {alpha}-adrenergic-induced increase of L-type calcium currents.

Conclusion: We found a new binding partner, ENH1, and a new target, {alpha}1C, for PKD1 in neonatal rat cardiomyocytes. We propose a model where ENH1 scaffolds PKD1 to {alpha}1C in order to form a signalling complex that regulates the activity of cardiac L-type voltage-gated Ca2+ channels.

KEYWORDS Protein kinases; Ca-channel; Signal transduction

Time for primary review: 31 days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 EndocrinologyHome page
A. Maturana, S. Lenglet, M. Python, S. Kuroda, and M. F. Rossier
Role of the T-Type Calcium Channel CaV3.2 in the Chronotropic Action of Corticosteroids in Isolated Rat Ventricular Myocytes
Endocrinology, August 1, 2009; 150(8): 3726 - 3734.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.