THE M(R)-35,000 BETA-ADRENERGIC-RECEPTOR MESSENGER-RNA-BINDING PROTEIN BINDS TRANSCRIPTS OF G-PROTEIN-LINKED RECEPTORS WHICH UNDERGO AGONIST-INDUCED DESTABILIZATION

被引:56
|
作者
THOLANIKUNNEL, BG
GRANNEMAN, JG
MALBON, CC
机构
[1] SUNY STONY BROOK, UNIV MED CTR, DEPT PHARMACOL, DIABET & METAB DIS RES PROGRAM, STONY BROOK, NY 11794 USA
[2] WAYNE STATE UNIV, DEPT PSYCHIAT, DETROIT, MI 48201 USA
关键词
D O I
10.1074/jbc.270.21.12787
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-ARE 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.
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页码:12787 / 12793
页数:7
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