Related Experiment Video

Updated: Jul 4, 2026

A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication
09:52

A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication

Published on: September 20, 2016

Regulation of insulin receptor substrate-1 expression levels by caveolin-1

Jia Chen1, Franco Capozza, An Wu

  • 1Thomas Jefferson University, Kimmel Cancer Center, Philadelphia, Pennsylvania, USA.

Journal of Cellular Physiology
|May 29, 2008
PubMed

Insights

Caveolin-1 (cav1) stabilizes insulin receptor substrate-1 (IRS-1) protein levels, crucial for cell growth. Loss of cav1 leads to IRS-1 degradation via the proteasome pathway.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Insulin receptor substrate-1 (IRS-1) is vital for cell proliferation and differentiation.
  • IRS-1 acts as a docking protein for the type 1 insulin-like growth factor receptor (IGF-IR).

Purpose of the Study:

  • To investigate the regulatory mechanism of IRS-1 expression.
  • To determine the role of caveolin-1 (cav1) in IRS-1 protein stability.

Main Methods:

  • Utilized mouse embryo fibroblasts (MEFs) with caveolin-1 gene deletion (KO cells).
  • Assessed IRS-1 mRNA and protein levels in wild-type and KO cells.
  • Re-introduced cav1 into KO cells to observe rescue effects.
  • Confirmed correlations in multiple cell lines and mouse tissues.
  • Investigated IRS-1 binding to cav1 using its phosphotyrosine binding (PTB) domain.
  • Examined IRS-1 degradation via the proteasome pathway.

Main Results:

  • IRS-1 expression is down-regulated in cav1-deficient cells, without affecting mRNA levels.
  • Re-introduction of cav1 restores IRS-1 expression, indicating a direct role.
  • A reciprocal stabilization and strict correlation between IRS-1 and cav1 protein levels were observed.
  • IRS-1 binds to tyrosine 14 of cav1, which is phosphorylated upon IGF-1 stimulation.
  • IRS-1 down-regulation in cav1-/- cells is mediated by the proteasome pathway.

Conclusions:

  • Identified a novel mechanism regulating IRS-1 protein expression through caveolin-1.
  • Caveolin-1 stabilizes IRS-1 protein levels, impacting cell proliferation and transformation.
  • This interaction is crucial for understanding IRS-1's role in cellular processes.

More Related Videos

Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay08:34

Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay

Published on: July 15, 2025

Related Concept Videos

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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
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...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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...