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Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure
- Source :
- Nature Medicine. Dec, 2003, Vol. 9 Issue 12, p1506, 7 p.
- Publication Year :
- 2003
-
Abstract
- Nitric oxide (NO) inhibits vascular contraction by activating cGMP-dependent protein kinase I-[alpha] (PKGI-[alpha]), which causes dephosphorylation of myosin light chain (MLC) and vascular smooth muscle relaxation. Here we show that PKGI-[alpha] attenuates signaling by the thrombin receptor protease-activated receptor-1 (PAR-1) through direct activation of regulator of G-protein signaling-2 (RGS-2). NO donors and cGMP cause cGMP-mediated inhibition of PAR-1 and membrane localization of RGS-2. PKGI-[alpha] binds directly to and phosphorylates RGS-2, which significantly increases GTPase activity of G[sub.q], terminating PAR-1 signaling. Disruption of the RGS-2-PKGI-[alpha] interaction reverses inhibition of PAR-1 signaling by nitrovasodilators and cGMP. Rgs2[sup.-/-] mice develop marked hypertension, and their blood vessels show enhanced contraction and decreased cGMP-mediated relaxation. Thus, PKGI-[alpha] binds to, phosphorylates and activates RGS-2, attenuating receptor-mediated vascular contraction. Our study shows that RGS-2 is required for normal vascular function and blood pressure and is a new drug development target for hypertension.<br />Author(s): Mary Tang [1]; Guang Wang [1]; Ping Lu [1, 4]; Richard H Karas [1]; Mark Aronovitz [1]; Scott P Heximer [2]; Kevin M Kaltenbronn [2]; Kendall J Blumer [2]; [...]
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 9
- Issue :
- 12
- Database :
- Gale General OneFile
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.193279110
- Full Text :
- https://doi.org/10.1038/nm958