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Am J Physiol Cell Physiol 283: C722-C734, 2002. First published April 24, 2002; doi:10.1152/ajpcell.00054.2002
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Vol. 283, Issue 3, C722-C734, September 2002

Polyamines regulate beta -catenin tyrosine phosphorylation via Ca2+ during intestinal epithelial cell migration

Xin Guo1,3, Jaladanki N. Rao1,3, Lan Liu1,3, Mort Rizvi1, Douglas J. Turner1,3, and Jian-Ying Wang1,2,3

Departments of 1 Surgery and 2 Pathology, University of Maryland School of Medicine and 3 Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201

Polyamines are essential for early mucosal restitution that occurs by epithelial cell migration to reseal superficial wounds after injury. Normal intestinal epithelial cells are tightly bound in sheets, but they need to be rapidly disassembled during restitution. beta -Catenin is involved in cell-cell adhesion, and its tyrosine phosphorylation causes disassembly of adhesion junctions, enhancing the spreading of cells. The current study determined whether polyamines are required for the stimulation of epithelial cell migration by altering beta -catenin tyrosine phosphorylation. Migration of intestinal epithelial cells (IEC-6 line) after wounding was associated with an increase in beta -catenin tyrosine phosphorylation, which decreased the binding activity of beta -catenin to alpha -catenin. Polyamine depletion by alpha -difluoromethylornithine reduced cytoplasmic free Ca2+ concentration ([Ca2+]cyt), prevented induction of beta -catenin phosphorylation, and decreased cell migration. Elevation of [Ca2+]cyt induced by the Ca2+ ionophore ionomycin restored beta -catenin phosphorylation and promoted migration in polyamine-deficient cells. Decreased beta -catenin phosphorylation through the tyrosine kinase inhibitor herbimycin-A or genistein blocked cell migration, which was accompanied by reorganization of cytoskeletal proteins. These results indicate that beta -catenin tyrosine phosphorylation plays a critical role in polyamine-dependent cell migration and that polyamines induce beta -catenin tyrosine phosphorylation at least partially through [Ca2+]cyt.

ornithine decarboxylase; cell adhesion; tyrosine kinase; alpha -catenin; intracellular calcium; restitution; intestinal epithelial cells


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