Abstract
The apical microvilli are closely related with the development and the maintenance of cell polarization, and the length of microvilli varies in a regular way among cell types. Ezrin, a member of the ezrin/radixin/moesin (ERM) family, seems to be involved in the formation and stabilization of the apical microvilli. We found that phosphorylation of ezrin caused elongation of microvilli via a p38 MAP-kinase signaling pathway in an immortalized mouse hepatic cell line. When, in the oncogenic Raf-1-transfected mouse hepatic cell line, epithelial to mesenchymal transition (EMT) indicated as down-regulation of E-cadherin and up-regulation of Snail occurred, loss of microvilli and down-regulation of ezrin but not radixin and moesin were also observed. In the Raf-1 transfectants treated with the MAP-kinase inhibitor PD98059 and the p38 MAP-kinase inhibitor SB203580, the numbers of microvilli and the expression of ezrin, E-cadherin and Snail were recovered. More interestingly, treatment with SB203580 induced elongation of microvilli and increased phosphorylation of ezrin (at Thr-567 and Tyr-353). Phosphorylated ezrin-positive dots were colocalized with actin-positive dots on the surface of some Raf-1 transfectants treated with SB203580. These results suggested that phosphorylation of ezrin via the p38 MAP-kinase signaling pathway might be involved in the formation of microvilli during development of epithelial cell polarization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acrylates / pharmacology
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Animals
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Cadherins / drug effects
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Cadherins / metabolism
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Cell Line
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Cell Proliferation / drug effects
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Chromones / pharmacology
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Cytoskeletal Proteins
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Down-Regulation
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Flavonoids / pharmacology
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Gene Expression Regulation, Enzymologic / drug effects
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Hepatocytes / cytology
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Hepatocytes / physiology*
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Imidazoles / pharmacology
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MAP Kinase Signaling System / physiology*
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Mice
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Microvilli / drug effects
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Microvilli / physiology
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Microvilli / ultrastructure*
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism
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Morpholines / pharmacology
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Phosphoproteins / drug effects
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Phosphoproteins / metabolism*
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Phosphorylation
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Proto-Oncogene Proteins c-raf / drug effects
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Proto-Oncogene Proteins c-raf / genetics
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Proto-Oncogene Proteins c-raf / metabolism
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Pyridines / pharmacology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Snail Family Transcription Factors
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Time Factors
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Transcription Factors / drug effects
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Transcription Factors / metabolism
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Up-Regulation
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Acrylates
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Cadherins
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Chromones
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Cytoskeletal Proteins
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Flavonoids
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Imidazoles
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Morpholines
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PD 150606
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Phosphoproteins
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Pyridines
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Snail Family Transcription Factors
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Transcription Factors
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ezrin
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Proto-Oncogene Proteins c-raf
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one