AT(1) receptor Gαq protein-independent signalling transcriptionally activates only a few genes directly, but robustly potentiates gene regulation from the β2-adrenergic receptor

Gitte L Christensen, Steen Knudsen, Mikael Schneider, Mark Aplin, Steen Gammeltoft, Søren P Sheikh, Jakob L Hansen, Mikael Schneider

Publikation: Bidrag til tidsskriftTidsskriftsartikelForskningpeer review


The angiotensin II type 1 receptor (AT(1)R) is known to signal through heterotrimeric G proteins, and Gαq protein-independent signalling has only recently gained appreciation for profound impact on a diverse range of biological functions. β-Arrestins, among other central mediators of Gαq protein-independent signalling from the AT(1)R interact with transcriptional regulators and promote phosphorylation of nuclear proteins. However, the relative contribution of Gαq protein-independent signalling in AT(1)R mediated transcriptional regulation remains elusive. We here present a comprehensive comparative analysis of Gαq protein-dependent and -independent regulation of AT(1)R mediated gene expression. We found angiotensin II to regulate 212 genes, whereas Gαq-independent signalling obtained with the biased agonist, SII angiotensin II only regulated few genes. Interestingly, SII angiotensin II, like Ang II vastly potentiated β2-adrenergic receptor-stimulated gene expression. These novel findings indicate that the Gαq protein-independent signalling mainly modifies the transcriptional response governed by other signalling pathways, while direct induction of gene expression by the AT(1)R is dependent on classical Gαq protein activation.

TidsskriftMolecular and Cellular Endocrinology
Udgave nummer1
Sider (fra-til)49-56
Antal sider8
StatusUdgivet - 1 jan. 2011