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

TY - JOUR

T1 - AT(1) receptor Gαq protein-independent signalling transcriptionally activates only a few genes directly, but robustly potentiates gene regulation from the β2-adrenergic receptor

AU - Christensen, Gitte Lund

AU - Knudsen, Steen

AU - Schneider, Mikael

AU - Aplin, Mark

AU - Gammeltoft, Steen

AU - Sheikh, Søren P

AU - Hansen, Jakob L

N1 - Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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.

AB - 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.

KW - Angiotensin II

KW - GTP-Binding Protein alpha Subunits, Gq-G11

KW - Gene Expression Regulation

KW - HEK293 Cells

KW - Humans

KW - Polymerase Chain Reaction

KW - Receptor, Angiotensin, Type 1

KW - Receptors, Adrenergic, beta-2

KW - Reproducibility of Results

KW - Response Elements

KW - Signal Transduction

KW - Time Factors

KW - Transcription Factors

KW - Transcription, Genetic

U2 - 10.1016/j.mce.2010.08.004

DO - 10.1016/j.mce.2010.08.004

M3 - Journal article

C2 - 20708651

SN - 0303-7207

VL - 331

SP - 49

EP - 56

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

IS - 1

ER -