In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 90, No. 1 ( 2002-01-11), p. 53-58
Abstract:
AT 1 receptor activation leads to vasoconstriction, blood pressure increase, free radical release, and cell growth. AT 1 receptor regulation contributes to the adaptation of the renin-angiotensin system to long-term stimulation and serves as explanation for the involvement of the AT 1 receptor in the pathogenesis of cardiovascular disease. The molecular mechanisms involved in AT 1 receptor regulation are poorly understood. Here, we report that angiotensin II accelerates AT 1 receptor mRNA decay in vascular smooth muscle cells. A cognate mRNA region within the 3′ untranslated region at bases 2175 to 2195 governs the inducible decay of the AT 1 receptor mRNA. Sequential protein purifications led to the discovery of a novel mRNA binding protein, calreticulin, which mediates destabilization of the AT 1 receptor mRNA. Angiotensin II–caused phosphorylation of calreticulin enables binding of calreticulin to the AT 1 receptor mRNA at bases 2175 to 2195 and propagates calreticulin-induced acceleration of AT 1 receptor mRNA decay. Thus, a novel mRNA binding protein, calreticulin, is discovered, which causes AT 1 receptor mRNA degradation via binding to a distinct mRNA region in the 3′ untranslated region. These findings display a novel mechanism of posttranscriptional mRNA processing.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/hh0102.102503
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2002
detail.hit.zdb_id:
1467838-X
