Article
The G protein-coupled receptor Mas constitutively activates the small GTPase RhoA in vascular cells
Der G Protein gekoppelte Rezeptor Mas aktiviert die kleine GTPase RhoA konstitutiv in Gefaesszellen
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Published: | August 8, 2006 |
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The Mas proto-oncogene is coding for a G protein-coupled receptor. We recently described angiotensin (Ang)-(1-7) as an endogenous ligand for the Mas receptor. This peptide opposes a variety of Ang II effects and thus stimulates e.g. the baroreflex and vasorelaxation. Our recent investigations also identified Mas to antagonize the AT1 receptor through physical interaction.
We thus investigated the effects on intracellular signalling by Ang-(1-7) in Mas-transfected cells. Surprisingly, all investigated Mas-transfected cell lines (e.g. endothelial cells, CHO, and HEK) demonstrated a ligand-independent constitutive activation of serum response element (SRE)-dependent gene transcription, which required the activation of the monomeric GTPase RhoA, but not Rac1. The Mas-induced RhoA activation was specifically mediated by Gq/11-proteins. Likewise, Mas constitutively induced phospholipase C activity. Mas-transfected NIH-3T3 cells exhibited an accelerated growth and increased foci formation. Both could be fully suppressed by dominant negative mutants of either Gq or RhoA.
Since the vasculature RhoA signalling pathways are intimately involved in the regulation of endothelial barrier function, inflammation, and transendothelial leukocyte migration, platelet activation, thrombosis and oxidative stress, as well as smooth muscle contraction, migration, proliferation and differentiation, the constitutive activation of RhoA by Mas could be of great interest as a new therapeutic target in cardiovascular diseases.