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Involvement of Phosphatidylinositol 3-Kinase and Mitogen-activated Protein Kinases in Glycine-extended Gastrin-induced Dissociation and Migration of Gastric Epithelial Cells

2001; Elsevier BV; Volume: 276; Issue: 44 Linguagem: Inglês

10.1074/jbc.m105090200

1083-351X

Frédéric Hollande, Armelle Choquet, Emmanuelle Blanc, Debra J. Lee, Jean-Pierre Balì, Graham S. Baldwin,

Pancreatic function and diabetes

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 gastrin17 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 gastrin17 stimulated proliferation of IMGE-5 cells via distinct receptors. Glycine-extended gastrin17-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 gastrin17 induced a PI3-kinase-mediated tyrosine phosphorylation of the adherens junction protein β-catenin, partial dissociation of the complex between β-catenin and the transmembrane protein E-cadherin, and delocalization of β-catenin into the cytoplasm. Long lasting activation of MAP kinases by glycine-extended gastrin17 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 gastrin17. 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 G17-Gly on the adhesion and migration of gastric epithelial cells.