The M(r) 35,000 beta-adrenergic receptor mRNA-binding protein binds transcripts of G-protein-linked receptors which undergo agonist-induced destabilization.
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.
Tholanikunnel
B G
BG
Department of Pharmacology, State University of New York, Stony Brook 11794-8651, USA.
Granneman
J G
JG
Malbon
C C
CC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001482:Base Composition; D006224:Cricetinae; D000242:Cyclic AMP / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis / Q000145:classification / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3; D018179:Receptors, Thrombin / Q000096:biosynthesis / Q000235:genetics*; D013045:Species Specificity; D013917:Thrombin / Q000494:pharmacology; D014649:Vas Deferens / Q000166:cytology
D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D018179:Receptors, Thrombin; D000242:Cyclic AMP; D013917:Thrombin; D019204:GTP-Binding Proteins