Signal transduction cascades triggered by EGF receptor activation: relevance to gastric injury repair and ulcer healing.
Growth factors and their receptors are known to play important roles in normal cell proliferation, tissue repair, and ulcer healing. Epidermal growth factor (EGF) inhibits acid secretion, protects gastric mucosa against injury, mediates mucosal adaptation, and accelerates gastroduodenal ulcer healing. EGF exerts its actions by binding to its receptor (EGF-R), which is a transmembrane protein tyrosine kinase. Binding of EGF to its receptor triggers receptor dimerization and autophosphorylation, recruitment of kinase substrates (signaling enzyme adapter proteins with an SH2 domain, Grb2 adapter protein, and Grb2-SOS complex). These events lead to Ras (GTP-binding protein) phosphorylation and activation of the Ras/Raf/MAP kinase pathway, in turn leading to phosphorylation of regulatory proteins and transcription factors and culminating in cell proliferation. Other pathways potentially activated by EGF include the phosphatidylinositol pathway (leading to activation of protein kinase C and an increase in cytosolic calcium) and the JAK/STAT signaling pathway. While EGF-induced signaling events have been extensively studied in various cell systems, predominantly neoplastic and/or transformed cells, the relevance of those findings to gastric mucosal injury repair or ulcer healing is as yet not fully elucidated. This paper is intended to provide an overview of signaling pathways triggered by EGF-R activation and on this background to summarize current knowledge pertaining to involvement of EGF-R signaling pathways in gastric mucosal repair and ulcer healing.
Pai
R
R
Department of Medicine/Gastroenterology, Veterans Administration Medical Center, Long Beach, California, USA.
Tarnawski
A
A
D000818:Animals; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005753:Gastric Mucosa / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013276:Stomach Ulcer / Q000201:enzymology / Q000378:metabolism*
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases