HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 36, 26340-26349, September 8, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/36/26340    most recent M605437200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Policha, A. Articles by Ferguson, S. S. G. Search for Related Content PubMed PubMed Citation Articles by Policha, A. Articles by Ferguson, S. S. G. Social Bookmarking                      What's this?

Role of Angiotensin II Type 1A Receptor Phosphorylation, Phospholipase D, and Extracellular Calcium in Isoform-specific Protein Kinase C Membrane Translocation Responses^*

Aleksandra Policha¹, Noriko Daneshtalab, Lina Chen^¶, Lianne B. Dale, Christophe Altier^¶2, Houman Khosravani^¶, Walter G. Thomas^||, Gerald W. Zamponi^¶3, and Stephen S. G. Ferguson, Holds a Canada Research Chair in molecular neurobiology and is a Career Investigator of the Heart and Stroke Foundation of Ontario⁴

From the Cell Biology Research Group, Robarts Research Institute, Department of Physiology and Pharmacology, The University of Western Ontario, 100 Perth Drive, London, Ontario N6A 5K8, Canada, ^¶Department of Physiology, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada, and ^||Baker Heart Research Institute, St. Kilda Road Central, Melbourne 8008, Australia

The angiotensin II type 1A receptor (AT_1AR) plays an important role in cardiovascular function and as such represents a primary target for therapeutic intervention. The AT_1AR is coupled via G_q to the activation of phospholipase C, the hydrolysis of phosphoinositides, release of calcium from intracellular stores, and the activation of protein kinase C (PKC). We show here that PKCI and PKCII exhibit different membrane translocation patterns in response to AT_1AR agonist activation. Whereas PKCII translocation to the membrane is transient, PKCI displays additional translocation responses: persistent membrane localization and oscillations between the membrane and cytosol following agonist removal. The initial translocation of PKCI requires the release of calcium from intracellular stores and the activation of phospholipase C, but persistent membrane localization is dependent upon extracellular calcium influx. The mutation of any of the three PKC phosphorylation consensus sites (Ser-331, Ser-338, and Ser-348) localized within the AT_1AR C-tail significantly increases the probability that persistent increases in diacylglycerol levels and PKCI translocation responses will be observed. The persistent increase in AT_1AR-mediated diacylglycerol formation is mediated by the activation of phospholipase D. Although the persistent PKCI membrane translocation response is absolutely dependent upon the PKC activity-dependent recruitment of an extracellular calcium current, it does not require the activation of phospholipase D. Taken together, we show that the patterning of AT_1AR second messenger response patterns is regulated by heterologous desensitization and PKC isoform substrate specificity.

Received for publication, June 6, 2006 , and in revised form, July 7, 2006.

^* This work was supported in part by Heart and Stroke Foundation of Ontario (HSFO) Grant T-5933 (to S. S. G. F.), HSFO Program Grant PRG-5967, and a Canadian Institutes of Health Research grant (to G. W. Z.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Recipient of an Ontario graduate studentship.

² Recipient of fellowships from the Alberta Heritage Foundation for Medical Research (AHFMR) and the Heart and Stroke Foundation of Canada.

³ An AHFMR Senior Scholar. Holds a Canada Research Chair in molecular neurobiology.

⁴ To whom correspondence should be addressed: Robarts Research Inst., 100 Perth Dr., P. O. Box 5015, London, Ontario N6A 5K8, Canada. Tel.: 519-663-3825; Fax: 519-663-3314; E-mail: ferguson{at}robarts.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?