Related Experiment Video

Updated: Jul 7, 2026

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
09:14

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes

Published on: June 13, 2014

Notch and integrin affinity: a sticky situation

Aly Karsan1

  • 1Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, British Columbia V6K 2Z4, Canada. akarsan@bccrc.ca

Science Signaling
|February 14, 2008
PubMed

Insights

The Notch pathway regulates cell fate and adhesion by enhancing beta(1) integrin affinity. This study reveals Notch activates R-Ras, a small GTP-binding protein, to increase vascular cell adhesion.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Notch pathway is crucial for intercellular signaling and cell fate determination in diverse tissues.
  • Aberrant Notch signaling is implicated in diseases such as cancer and cardiovascular disorders.
  • Notch signaling influences cell proliferation, survival, migration, and differentiation.

Purpose of the Study:

  • To elucidate the molecular mechanism by which Notch activation enhances vascular endothelial cell adhesion.
  • To investigate the role of the small GTP-binding protein R-Ras in Notch-mediated integrin affinity modulation.
  • To explore the potential noncanonical pathways involved in Notch-R-Ras signaling.

Main Methods:

  • Investigated Notch-dependent changes in beta(1) integrin affinity for extracellular matrix proteins.
  • Utilized biochemical assays to assess the activation state of R-Ras in response to Notch signaling.
  • Examined the interplay between Notch, R-Ras, and H-Ras in regulating integrin function.
  • Explored CSL-independent signaling pathways in Notch-R-Ras activation.

Main Results:

  • Notch activation enhances beta(1) integrin affinity for fibronectin, collagens I and IV, and vitronectin without changing integrin surface levels.
  • This increase in integrin affinity is mediated by the activation of R-Ras.
  • Notch-dependent R-Ras activation appears to counteract H-Ras-mediated suppression of integrin affinity.
  • R-Ras activation by Notch may occur via a CSL-independent pathway.

Conclusions:

  • Notch signaling regulates vascular cell adhesion through R-Ras-dependent enhancement of beta(1) integrin affinity.
  • The findings highlight a novel noncanonical pathway for Notch signaling in vascular cells.
  • Understanding Notch-R-Ras interactions is critical for deciphering Notch's role in vascular biology and disease.

More Related Videos

A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs04:15

A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs

Published on: February 2, 2024

Tension Gauge Tether Probes for Quantifying Growth Factor Mediated Integrin Mechanics and Adhesion09:56

Tension Gauge Tether Probes for Quantifying Growth Factor Mediated Integrin Mechanics and Adhesion

Published on: February 11, 2022

Related Concept Videos

Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Anchoring Junctions01:03

Anchoring Junctions

Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...