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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Crosstalk between PI3 kinase/PDK1/Akt/Rac1 and Ras/Raf/MEK/ERK pathways downstream PDGF receptor

Emma Tabe Eko Niba1, Hisao Nagaya, Takeshi Kanno

  • 1Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|July 3, 2013
PubMed
Abstract

Insights

This study reveals a reciprocal activation loop between the PI3K/Akt and Ras/MEK/ERK pathways in mesothelioma cells. These findings elucidate key signaling crosstalk critical for cancer cell behavior.

Area of Science:

  • Oncology
  • Cell Signaling
  • Molecular Biology

Background:

  • Malignant mesothelioma cell growth and migration are influenced by signaling pathways.
  • Previous research suggested crosstalk between IRS/PI3K/Akt and Ras/MEK/ERK pathways downstream of the PDGF-ββ receptor.

Purpose of the Study:

  • To provide evidence for the crosstalk between the IRS/PI3K/Akt/Rac1/ROCK and Ras/Raf/MEK/ERK pathways in malignant mesothelioma cells.
  • To investigate the activation mechanisms of Akt, MEK, and ERK in MSTO-211H cells.

Main Methods:

  • Western blotting was used to assess the activation of Akt, MEK, and ERK in MSTO-211H cells.
  • RNA interference (siRNA) was employed to knock down key proteins including Akt, PI3 kinase, PDK1, and Rac1.
  • Förster Resonance Energy Transfer (FRET) was utilized to monitor Rac1 activity in live and fixed cells.

Main Results:

  • Basal activation of ERK, Akt, and Rac1 was observed in MSTO-211H cells.
  • Inhibition or knockdown of PI3 kinase, PDK1, Akt, and Rac1 suppressed ERK activation.
  • MEK and ERK inhibitors reduced Akt and Rac1 activation, indicating a reciprocal signaling loop.

Conclusions:

  • ERK activation is dependent on PI3 kinase, PDK1, Akt, and Rac1.
  • Akt and Rac1 activation can be influenced by MEK and ERK signaling.
  • These findings highlight a complex crosstalk essential for mesothelioma cell function.

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