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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

Activation of Raf-1 during experimental gastric ulcer healing is Ras-mediated and protein kinase C-independent

R Pai1, M K Jones, M Tomikawa

  • 1Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California, USA.

The American Journal of Pathology
|November 7, 1999
PubMed

Insights

Gastric ulcer healing involves increased Raf-1 kinase activity, mediated by Ras and adapter proteins like Shc-Grb2-Sos. This process is independent of protein kinase C (PKC) and linked to epidermal growth factor receptor (EGF-R) signaling.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • Gastroenterology

Background:

  • Previous studies showed increased epidermal growth factor receptor (EGF-R) phosphorylation and kinase activities during gastric ulcer healing.
  • The intermediate signaling pathways linking activated receptor tyrosine kinases to extracellular signal-regulated kinases (ERKs) in ulcer healing remain unclear.

Purpose of the Study:

  • To investigate the role of Raf-1 kinase, its activators (Ras, protein kinase C [PKC]), and adapter proteins (Shc, Grb2, Sos) in experimental gastric ulcer healing.
  • To determine if Raf-1 and ERK activation during healing is epithelial-cell dependent and mediated by Ras or PKC.

Main Methods:

  • Assessed Raf-1 activity, PKC and Ras levels, and Shc, Grb2, Sos complex formation in experimental gastric ulcer margins.
  • Utilized a rat gastric epithelial cell line (RGM1) to study the effects of epidermal growth factor (EGF) on PKC, Ras, and ERK activities.

Main Results:

  • Gastric ulceration significantly increased Raf-1 kinase activity, Grb2 and Ras protein levels, and Shc-Grb2 and Grb2-Sos complex formation.
  • PKC activity and protein levels were significantly decreased in ulcer margins.
  • In RGM1 cells, EGF stimulated Ras and ERK2 activity but not PKC activity.

Conclusions:

  • Raf-1 activation during gastric ulcer healing is primarily Ras-mediated and involves the Shc-Grb2-Sos signaling complex.
  • The observed Raf-1 activation is independent of PKC and likely occurs within the epithelial component of the ulcer margin.

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