Phosphorylation of ezrin enhances microvillus length via a p38 MAP-kinase pathway in an immortalized mouse hepatic cell line.
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.
Lan
Mengdong
M
Department of Pathology, Sapporo Medical University School of Medicine, S1. W17. Sapporo 060-8556, Japan.
Kojima
Takashi
T
Murata
Masaki
M
Osanai
Makoto
M
Takano
Ken-ichi
K
Chiba
Hideki
H
Sawada
Norimasa
N
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
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