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The M(r) 35,000 beta-adrenergic receptor mRNA-binding protein binds transcripts of G-protein-linked receptors which
B G Tholanikunnel1, J G Granneman, C C Malbon
1Department of Pharmacology, State University of New York, Stony Brook 11794-8651, USA.
Abstract:
The M(r) 35,000 beta-adrenergic receptor mRNA-binding protein, termed beta-ARB protein, is induced by beta-adrenergic agonists and binds to beta 2-receptor mRNAs that display agonist-induced destabilization. Recently a cognate sequence in the mRNA was identified that provides for recognition by beta-ARB protein. In the present work we test the ability of the beta-ARB to discriminate among G-protein-linked receptor mRNAs that either do or do not display agonist-induced destabilization and test the predictive value of the presence of the cognate sequence to identify receptors displaying post-transcriptional regulation. Transcripts of beta 2-, but not rat beta 1-, rat beta 3-, or human beta 3- adrenergic receptors bind beta-ARB protein, linking agonist-induced destabilization of mRNA to transcripts with the cognate sequence. Scanning GeneBank for G-protein-linked receptor transcripts with the cognate sequence revealed several candidates, including the thrombin receptor. We demonstrate that the thrombin receptor mRNA is recognized by beta-ARB protein and like the beta 2-receptor is regulated post-transcriptionally by agonist and cAMP. Thus, the domain of regulation by beta-ARB protein includes transcripts of G-protein-linked receptors other than beta 2-adrenergic receptors.