Related Experiment Video

Updated: Aug 12, 2026

Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
07:21

Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice

Published on: September 28, 2015

Angiotensin II stimulates sis-inducing factor-like DNA binding activity. Evidence that the AT1A receptor activates

G J Bhat1, T J Thekkumkara, W G Thomas

  • 1Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822.

The Journal of Biological Chemistry
|December 16, 1994
PubMed

Insights

Angiotensin II activates the Stat91 signaling pathway, a direct link from cell surface receptors to nuclear genes. This discovery reveals how G-protein-coupled receptors influence gene transcription.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Gene transcription regulation

Background:

  • The Stat91 pathway directly links cell surface receptors to nuclear target genes.
  • This pathway involves tyrosine phosphorylation, nuclear translocation of DNA binding factors, and interaction with regulatory elements.
  • Members of the STAT family of transcription factors are key components of the sis-inducing factor (SIF) complex.

Purpose of the Study:

  • To investigate whether angiotensin II (AII), a known growth factor, can activate the Stat91 pathway.
  • To explore the role of angiotensin type 1A (AT1A) receptors in this signaling cascade.

Main Methods:

  • Utilized neonatal rat cardiac fibroblasts and CHO-K1 cells expressing specific AII receptors.
  • Assessed SIF-like activity and DNA binding to the sis-inducing element (SIE) after AII stimulation.
  • Examined the effect of protein synthesis inhibitors and tyrosine kinase inhibitors (genistein) on SIF activity.
  • Identified Stat91 or related proteins within the AII-induced SIF complex using Western blot analysis.

Main Results:

  • Angiotensin II induced SIF-like activity in both cell types, peaking at 2-3 hours.
  • DNA binding activity to SIE was detected in cytoplasmic and nuclear fractions following AII exposure.
  • The induced SIF activity was resistant to protein synthesis inhibitors but sensitive to genistein.
  • Stat91 was identified as a component of the AII-induced SIF complex, with increased tyrosine phosphorylation observed in nuclear extracts.

Conclusions:

  • This study provides the first evidence that the AT1A receptor, a seven-transmembrane, G-protein-coupled receptor, activates the Stat91 nuclear signaling pathway.
  • Angiotensin II signaling through AT1A receptors influences gene transcription via the Stat91 pathway.
  • The findings elucidate a novel mechanism of G-protein-coupled receptor-mediated gene regulation.

More Related Videos

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors12:03

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors

Published on: June 7, 2016

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation09:40

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation

Published on: June 27, 2017

Related Concept Videos

Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...