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Related Experiment Videos

Integrin-mediated cell adhesion activates mitogen-activated protein kinases

Q Chen1, M S Kinch, T H Lin

  • 1Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599.

The Journal of Biological Chemistry
|October 28, 1994
PubMed
Summary

Cell adhesion via integrins activates mitogen-activated protein (MAP) kinases, crucial for cell growth and gene expression. This process involves the cytoskeleton and leads to MAP kinase nuclear translocation.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Integrins are signal-transducing receptors modulating cell growth and gene expression.
  • Integrin signaling involves cytoplasmic tyrosine kinases like pp125FAK.
  • Extracellular matrix interactions regulate cellular functions.

Purpose of the Study:

  • Investigate novel aspects of integrin-mediated signal transduction.
  • Determine if cell adhesion to extracellular matrix proteins activates mitogen-activated protein (MAP) kinases.
  • Elucidate the role of the cytoskeleton in integrin-induced signaling.

Main Methods:

  • Utilized 3T3 and REF52 fibroblasts.
  • Studied cell adhesion to substrates coated with extracellular matrix proteins (fibronectin, laminin) and synthetic peptides (RGD sequence).

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  • Assessed MAP kinase activation and translocation, and the effect of cytochalasin D on signaling.

    • Main Results:

    • Cell adhesion to integrin ligands (fibronectin, laminin, RGD peptide) activated MAP kinases.
    • MAP kinase activation depended on integrin engagement, not just cell attachment.
    • Cytochalasin D treatment blocked adhesion-induced MAP kinase activation, highlighting cytoskeleton involvement.
    • Activated MAP kinases translocated to the nucleus in REF52 cells.

    Conclusions:

    • Integrin-mediated cell adhesion is a sufficient stimulus for MAP kinase activation and nuclear translocation.
    • This signaling pathway has implications for extracellular matrix regulation of cell growth and differentiation.
    • The cytoskeleton plays a critical role in transmitting adhesion signals to MAP kinases.