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 -