Document Detail

Polyamines regulate beta-catenin tyrosine phosphorylation via Ca(2+) during intestinal epithelial cell migration.
MedLine Citation:
PMID:  12176729     Owner:  NLM     Status:  MEDLINE    
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).
Xin Guo; Jaladanki N Rao; Lan Liu; Mort Rizvi; Douglas J Turner; Jian-Ying Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  283     ISSN:  0363-6143     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-08-14     Completed Date:  2002-09-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C722-34     Citation Subset:  IM    
Department of Surgery, University of Maryland School of Medicine, Baltimore 21201, USA.
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MeSH Terms
Biogenic Polyamines / metabolism,  pharmacology*
Blotting, Western
Cadherins / metabolism
Calcium / metabolism*
Cell Line
Cell Movement / drug effects,  physiology
Cytoskeletal Proteins / metabolism*
Eflornithine / pharmacology
Enzyme Inhibitors / pharmacology
Intestinal Mucosa / cytology,  drug effects*,  metabolism*
Intracellular Fluid / metabolism
Ionophores / pharmacology
Macromolecular Substances
Microfilaments / drug effects,  metabolism
Phosphorylation / drug effects
Protein-Tyrosine Kinases / antagonists & inhibitors
Trans-Activators / metabolism*
Tyrosine / metabolism
beta Catenin
Grant Support
Reg. No./Substance:
0/Biogenic Polyamines; 0/Cadherins; 0/Catnb protein, rat; 0/Cytoskeletal Proteins; 0/Enzyme Inhibitors; 0/Ionophores; 0/Macromolecular Substances; 0/Trans-Activators; 0/beta Catenin; 55520-40-6/Tyrosine; 70052-12-9/Eflornithine; 7440-70-2/Calcium; EC Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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