Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats

Gastroenterology. 1998 Apr;114(4):706-13. doi: 10.1016/s0016-5085(98)70584-0.


Background & aims: Previous studies have shown that gastric ulceration stimulates epithelial cell proliferation and overexpression of epidermal growth factor (EGF) and EGF receptor (EGF-R) in the mucosa bordering necrosis. The aim of this study was to investigate whether extracellular signal-regulated kinase (ERK) cascade is involved in the healing of experimental gastric ulcers.

Methods: We studied EGF-R levels, EGF-R phosphorylation levels, and ERK1 and ERK2 activity in normal and ulcerated rat gastric mucosa. We also examined the effect of Tyrphostin A46 (potent inhibitor of EGF-R and EGF-R kinase-dependent proliferation) on the above parameters.

Results: During the initial stages of healing (3 and 7 days), ulcerated mucosa showed significant increase (vs. controls) in protein tyrosine kinase activity, EGF-R levels (510% and 550%), EGF-R phosphorylation levels, ERK1 activity (430% and 880%), and ERK2 activity (550% and 990%). Tyrphostin A46 treatment significantly inhibited ulcer healing and reduced EGF-R levels, EGF-R phosphorylation, and ERK1 and ERK2 activity.

Conclusions: These findings indicate that experimental gastric ulcer healing involves activation of EGF-R-ERK signal transduction pathway.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Benzylidene Compounds / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • ErbB Receptors / analysis
  • Male
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Nitriles / pharmacology
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction*
  • Stomach Ulcer / enzymology*
  • Tyrosine / metabolism
  • Tyrphostins*


  • Benzylidene Compounds
  • Nitriles
  • Tyrphostins
  • tyrphostin A46
  • Tyrosine
  • ErbB Receptors
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases