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Up-regulation of caveolin attenuates epidermal growth factor signaling in senescent cells

W Y Park1, J S Park, K A Cho

  • 1Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea.

The Journal of Biological Chemistry
|April 27, 2000
PubMed

Insights

Senescent cells resist epidermal growth factor (EGF) signaling due to increased caveolin proteins, which bind to EGF receptors and block Erk-1/2 activation. This mechanism appears independent of aging itself.

Area of Science:

  • Cellular senescence
  • Molecular biology
  • Aging research

Background:

  • Senescent human diploid fibroblasts exhibit unresponsiveness to growth factors like epidermal growth factor (EGF).
  • Despite normal receptor levels, downstream signaling is attenuated in senescent cells.
  • The precise mechanism behind this signaling attenuation remains unclear.

Purpose of the Study:

  • To investigate the mechanism of signaling attenuation in senescent fibroblasts upon EGF stimulation.
  • To determine the role of Erk-1/2 phosphorylation and caveolin proteins in EGF unresponsiveness.
  • To explore the relationship between caveolin expression and aging phenotypes.

Main Methods:

  • EGF stimulation assays in senescent and young fibroblasts.
  • Analysis of Erk-1/2 phosphorylation.
  • Investigation of caveolin protein levels and interactions with EGF receptors using electron microscopy.
  • Examination of caveolin expression in aged rat tissues.
  • Overexpression of caveolin-1 in young fibroblasts.

Main Results:

  • Senescent cells failed to phosphorylate Erk-1/2 after EGF stimulation, unlike young cells.
  • Increased caveolin protein levels and enhanced interactions between caveolin-1 and EGF receptors were observed in senescent cells.
  • A higher number of caveolae structures were detected in senescent cells.
  • Caveolin proteins increased in aged rat tissues (brain, spleen, lung).
  • p53-induced senescence did not involve caveolin-1 induction, and Erk-1/2 phosphorylation remained normal.
  • Overexpression of caveolin-1 in young fibroblasts suppressed Erk-1/2 activation by EGF.

Conclusions:

  • Overexpression of caveolins contributes to the unresponsiveness of senescent fibroblasts to EGF stimulation.
  • This mechanism of signaling attenuation appears independent of growth arrest and other aging phenotypes.
  • Caveolin-mediated inhibition of EGF signaling is a key factor in cellular aging.

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