title: Involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinases in glycine-extended gastrin-induced dissociation and migration of gastric epithelial cells.
abstract: The various molecular forms of gastrin can act as promoters of proliferation and differentiation in different regions of the gastrointestinal tract. We report a novel stimulatory effect of glycine-extended gastrin(17) only on cell/cell dissociation and cell migration in a non-tumorigenic mouse gastric epithelial cell line (IMGE-5). In contrast, both amidated and glycine-extended gastrin(17) stimulated proliferation of IMGE-5 cells via distinct receptors. Glycine-extended gastrin(17)-induced dissociation preceded migration and was blocked by selective inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) but did not require mitogen-activated protein (MAP) kinase activation. Furthermore, glycine-extended gastrin(17) induced a PI3-kinase-mediated tyrosine phosphorylation of the adherens junction protein beta-catenin, partial dissociation of the complex between beta-catenin and the transmembrane protein E-cadherin, and delocalization of beta-catenin into the cytoplasm. Long lasting activation of MAP kinases by glycine-extended gastrin(17) was specifically required for the migratory response, in contrast to the involvement of a rapid and transient MAP kinase activation in the proliferative response to both amidated and glycine-extended gastrin(17). Therefore, the time course of MAP kinase activation appears to be a critical determinant of the biological effects mediated by this pathway. Together with the involvement of PI3-kinase in the dissociation of adherens junctions, long term activation of MAP kinases seems responsible for the selectivity of this novel effect of G(17)-Gly on the adhesion and migration of gastric epithelial cells.
authors.affiliation: Laboratoire de Signalisation Cellulaire Normale et Tumorale, EA MNRT 2995, Faculté de Pharmacie, Montpellier 34060, France.
authors.forename: F
authors.initials: F
authors.lastname: Hollande
authors.forename: A
authors.initials: A
authors.lastname: Choquet
authors.forename: E M
authors.initials: EM
authors.lastname: Blanc
authors.forename: D J
authors.initials: DJ
authors.lastname: Lee
authors.forename: J P
authors.initials: JP
authors.lastname: Bali
authors.forename: G S
authors.initials: GS
authors.lastname: Baldwin
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D005755:Gastrins / Q000494:pharmacology*; D005998:Glycine / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015534:Trans-Activators; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin
chemical_list: D003598:Cytoskeletal Proteins; D005755:Gastrins; D015534:Trans-Activators; D051176:beta Catenin; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D005998:Glycine