Polyamines regulate beta-catenin tyrosine phosphorylation via Ca(2+) during intestinal epithelial cell migration.
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 Ca(2+) concentration ([Ca(2+)](cyt)), prevented induction of beta-catenin phosphorylation, and decreased cell migration. Elevation of [Ca(2+)](cyt) induced by the Ca(2+) 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 [Ca(2+)](cyt).
Guo
Xin
X
Department of Surgery, University of Maryland School of Medicine, Baltimore 21201, USA.
Rao
Jaladanki N
JN
Liu
Lan
L
Rizvi
Mort
M
Turner
Douglas J
DJ
Wang
Jian-Ying
JY
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D046911:Macromolecular Substances; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin
D015317:Biogenic Polyamines; D015820:Cadherins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D007476:Ionophores; D046911:Macromolecular Substances; D015534:Trans-Activators; D051176:beta Catenin; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D002118:Calcium; D000518:Eflornithine