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


INABIS '98 Home Page Your Symposium Related Symposia & Posters Scientific Program Exhibitors' Foyer Personal Itinerary New Search

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)


 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. 

 Back to the top.
Presentation Number SAmurphy0298
Keywords: protein kinase A, mRNA stability, retrovirus, signal transduction, down regulation

| Discussion Board | Next Page | Your Symposium |
© 1998 Author(s) Hold Copyright