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Invited
Symposium
Presentation
 
 
 
 
 

Abstract

Introduction

mRNA Content and Cell Surface AT1-R Levels

Protein Kinae A controls AT1-R mRNA stability

Mechansims of AT1-R mRNA Destabilization

Acknowledgements, References and Reprints
 

Discussion
Board

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Regulation of AT1 Angiotensin Receptor Gene Expression in Vascular Smooth Muscle Cells
T.J. Murphy (Department of Pharmacology, Emory University, Atlanta, USA)

Contact Person: TJ Murphy (tmurphy@pharm.emory.edu)


Abstract

 Several classes of agonists down regulate AT1-receptor gene expression in rat vascular smooth muscle cells (VSMC). This is associated with a fairly rapid loss of the AT1-R mRNA. New studies in VSMC provide direct evidence that regulation of AT1-R mRNA levels is a dominant pathway for specification of cell surface AT1-R protein levels. Agonists of growth factor and Gq-coupled receptors inhibit transcription of the AT1-R gene, but little is understood about how this occurs mechanistically. However, this effect alone cannot fully explain the loss of mRNA stimulated by agonists. Cyclic AMP-elevating agents do not affect VSMC AT1-R gene transcription, and protein kinase A mediated destabilization of the AT1-R mRNA contributes substantially to AT1-R down regulation by some, but not all classes of agonists. Powerful new systems, including a retroviral tetracycline regulated vector, have been created to express recombinant AT1-R minigenes in VSMC. With these, post-transcriptional processes can be experimentally separated from the complications of transcriptional effects by agonists on the native gene. Their use is accelerating our understanding of the mechanisms underlying signaling-regulated AT1-R mRNA stability control in VSMC. 

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Presentation Number SAmurphy0298
Keywords: protein kinase A, mRNA stability, retrovirus, signal transduction, down regulation


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