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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Active erk regulates microtubule stability in H-ras-transformed cells

R E Harrison1, E A Turley

  • 1Department of Anatomy and Cell Biology, University of Toronto, Toronto, Ontario, Canada M5G 1X8.

Neoplasia (New York, N.Y.)
|November 1, 2001
PubMed

Insights

Activated extracellular signal-regulated kinase (ERK) associates with microtubules (MTs), influencing their stability. This interaction, particularly with mutant H-ras, impacts cell proliferation and invasion.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Extracellular signal-regulated kinase (ERK) activation regulates cellular functions through various mechanisms.
  • Non-transcriptional roles of ERK in cell function are increasingly recognized.

Purpose of the Study:

  • To investigate the association of ERK with microtubules (MTs) and its role in MT stability.
  • To determine if activated ERK influences MT stability independently of gene transcription.

Main Methods:

  • Immunofluorescence microscopy to visualize ERK localization on MTs and mitotic spindles.
  • Cellular assays to assess MT stability.
  • Pharmacological inhibition (PD98059) and genetic manipulation (dominant-negative MKK1) to study pathway involvement.

Main Results:

  • Activated ERK was found to associate with MTs and mitotic spindles in fibroblasts and epithelial cells.
  • A higher proportion of activated ERK associated with MTs in cells expressing mutant active H-ras.
  • Ras pathway activation correlated with decreased MT stability, an effect blocked by MKK1 inhibition.
  • MKK1 inhibition did not alter ERK-MT association or parental cell MT stability.

Conclusions:

  • A subset of active ERK kinase associated with MTs contributes to MT instability in the presence of mutant active H-ras.
  • This MT-associated ERK likely plays a role in the enhanced invasive and proliferative capabilities of cells with mutant active H-ras.

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