Related Experiment Video

Updated: Oct 16, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Functional trans-inactivation of insulin receptor kinase by growth-inhibitory angiotensin II AT2 receptor

N Elbaz1, K Bedecs, M Masson

  • 1Institut Cochin de Génétique Moléculaire, Centre Nationale de la Recherche Scientifique UPR 0415, Paris, France.

Molecular Endocrinology (Baltimore, Md.)
|June 10, 2000
PubMed

Insights

Angiotensin II type 2 (AT2) receptors negatively impact insulin signaling by inhibiting insulin receptor (IR) activity. This cross-talk disrupts key pathways, affecting cell growth and function.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Endocrinology

Background:

  • Insulin and Angiotensin II Type 2 (AT2) receptors are critical cell surface proteins.
  • Cross-talk between different receptor families can significantly alter cellular responses.
  • Understanding these interactions is key to deciphering complex signaling networks.

Purpose of the Study:

  • To investigate the intracellular cross-talk between AT2 and insulin receptors.
  • To elucidate the mechanism by which AT2 receptor stimulation affects insulin signaling.
  • To determine the functional consequences of this receptor interaction.

Main Methods:

  • Utilized transfected Chinese hamster ovary (CHO-hAT2) cells and endogenous receptors in neuroblastoma and pancreatic cells.
  • Assessed insulin receptor (IR) tyrosine phosphorylation and autophosphorylating tyrosine kinase activity.
  • Examined insulin receptor substrate-1 (IRS-1) and SIRPalpha1 phosphorylation and SHP-2 association.

Main Results:

  • AT2 receptor stimulation inhibited insulin-induced extracellular signal-regulated protein kinase (ERK2) activity and cell proliferation.
  • AT2 receptor impaired the tyrosine phosphorylation of the IR beta-chain, a crucial early step in insulin signaling.
  • This inhibition of IR kinase activity led to reduced IRS-1 and SIRPalpha1 phosphorylation and subsequent SHP-2 binding.

Conclusions:

  • AT2 receptors functionally trans-inactivate the insulin receptor kinase.
  • This represents a novel mechanism of negative communication between G protein-coupled receptors and receptor tyrosine kinases.
  • The findings reveal a new layer of complexity in cellular signaling regulation.

More Related Videos

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance09:48

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance

Published on: February 17, 2023

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

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
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...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: