title: Phosphorylation of ezrin enhances microvillus length via a p38 MAP-kinase pathway in an immortalized mouse hepatic cell line.
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.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, S1. W17. Sapporo 060-8556, Japan.
authors.forename: Mengdong
authors.initials: M
authors.lastname: Lan
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Masaki
authors.initials: M
authors.lastname: Murata
authors.forename: Makoto
authors.initials: M
authors.lastname: Osanai
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Takano
authors.forename: Hideki
authors.initials: H
authors.lastname: Chiba
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
mesh_terms: D000179:Acrylates / Q000494:pharmacology; D000818:Animals; D015820:Cadherins / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003598:Cytoskeletal Proteins; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008871:Microvilli / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000071250:Snail Family Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000099149:Ezrin
chemical_list: D000179:Acrylates; D015820:Cadherins; D002867:Chromones; D003598:Cytoskeletal Proteins; D005419:Flavonoids; D007093:Imidazoles; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D010750:Phosphoproteins; D019908:Proto-Oncogene Proteins c-raf; D011725:Pyridines; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; D000099149:Ezrin; C100442:PD 150606; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one