Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands

Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1042-6. doi: 10.1073/pnas.98.3.1042. Epub 2001 Jan 23.

Abstract

The aim of this study is to elucidate the role of integrins in transducing fluid shear stress into intracellular signals in vascular endothelial cells, a fundamental process in vascular biology. We demonstrated that shear stress activates specific integrins in endothelial cells plated on substrates containing the cognate extracellular matrix (ECM) ligands. The shear stress-induced mechanotransduction, as manifested by integrin-Shc association, was abolished when new integrin-ECM ligand interactions were prevented by either blocking the integrin-binding sites of ECM ligands or conjugating the integrins to immobilized antibodies. Our results indicate that the dynamic formation of new connections between integrins and their specific ECM ligands is critical in relaying the signals induced by shear stress to intracellular pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport*
  • Antigens, CD / physiology
  • Cells, Cultured
  • Collagen / physiology
  • Endothelium, Vascular / physiology*
  • Extracellular Matrix / physiology*
  • Extracellular Matrix Proteins / physiology*
  • Fibrinogen / physiology
  • Fibronectins / physiology
  • Humans
  • Integrin beta1 / physiology
  • Integrin beta3
  • Integrins / physiology*
  • JNK Mitogen-Activated Protein Kinases
  • Laminin / physiology
  • Ligands
  • Mitogen-Activated Protein Kinases / metabolism
  • Platelet Membrane Glycoproteins / physiology
  • Proteins / metabolism
  • Receptors, Vitronectin / physiology*
  • Shc Signaling Adaptor Proteins
  • Signal Transduction / physiology*
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Stress, Mechanical
  • Umbilical Veins
  • Vitronectin / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Antigens, CD
  • Extracellular Matrix Proteins
  • Fibronectins
  • Integrin beta1
  • Integrin beta3
  • Integrins
  • Laminin
  • Ligands
  • Platelet Membrane Glycoproteins
  • Proteins
  • Receptors, Vitronectin
  • SHC1 protein, human
  • Shc Signaling Adaptor Proteins
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Vitronectin
  • Fibrinogen
  • Collagen
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases