title: Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pai
authors.forename: M
authors.initials: M
authors.lastname: Ohta
authors.forename: R M
authors.initials: RM
authors.lastname: Itani
authors.forename: I J
authors.initials: IJ
authors.lastname: Sarfeh
authors.forename: A S
authors.initials: AS
authors.lastname: Tarnawski
mesh_terms: D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D066246:ErbB Receptors / Q000032:analysis; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013276:Stomach Ulcer / Q000201:enzymology*; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins
chemical_list: D001597:Benzylidene Compounds; D009570:Nitriles; D020032:Tyrphostins; C086599:tyrphostin A46; D014443:Tyrosine; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases