AT receptor Gαq protein-independent signalling transcriptionally activates only a few genes directly, but robustly potentiates gene regulation from the β-2Adrenergic receptor

Gitte L. Christensen (1, 2) , Steen Knudsen (3) , Mikael Schneider (4) , Mark Aplin (1, 5) , Steen Gammeltoft (2) , Søren P. Sheikh (4) , Jakob L. Hansen (1, 6)

1 Department of Biomedical Sciences [Copenhagen]
2 Department of Clinical Biochemistry
3 Medical Prognostic Institute
4 Department for Clinical Biochemistry & Pharmacology
5 Victor Chang Cardiac Research Institute
6 Rigshospitalet [Copenhagen]

The Angiotensin II type 1 receptor (ATR) 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 ATR interact with transcriptional regulators and promote phosphorylation of nuclear proteins. However, the relative contribution of Gαq protein-independent signalling in ATR mediated transcriptional regulation remains elusive. We here present a comprehensive comparative analysis of Gαq protein-dependent and-independent regulation of ATR 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 β-2-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 ATR is dependent on classical Gαq protein activation.

Mots clés: Angiotensin II type 1 receptor; Gene expression; Microarray; Biased agonist; 7TMR; transcription factor

Gitte L. Christensen, Steen Knudsen, Mikael Schneider, Mark Aplin, Steen Gammeltoft, et al.. AT receptor Gαq protein-independent signalling transcriptionally activates only a few genes directly, but robustly potentiates gene regulation from the β-2Adrenergic receptor. Molecular and Cellular Endocrinology, 2010, ⟨10.1016/j.mce.2010.08.004⟩. ⟨hal-00639770⟩