14-3-3 protein family members have a regulatory role in retinoic acid-mediated induction of cytokeratins in F9 cells.
We have found that the expression of five 14-3-3 protein isoforms is induced during the retinoic acid (RA)-mediated differentiation of mouse embryonal carcinoma F9 cells. The induced expression of the 14-3-3 proteins is presumed to have a role in enhancing the mitogen-activated protein kinase (MAPK) activity during RA-mediated F9 cell differentiation, because using genetically engineered budding yeast we showed that these isoforms enhanced the signaling in the MAPK cascade mainly through the interaction with Raf-1. Then we assessed the role of increased MAPK activity in F9 cell differentiation by interfering with signaling in the MAPK cascade in F9 cells. The exogenous expression of dominant-negative MEK1 efficiently abrogated RA-mediated induction of the cytokeratins EndoA and EndoC in the F9 cells. These results suggest that the 14-3-3 proteins play a role in the efficient induction of the cytokeratins during F9 cell differentiation through their signal enhancing activity in the MAPK cascade.
Takihara
Y
Y
Department of Medical Genetics and Molecular Cell Biology, Department of Developmental Medicine, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, USA. takihara@biken.osaka-u.ac.jp
Matsuda
Y
Y
Irie
K
K
Matsumoto
K
K
Hara
J
J
D048948:14-3-3 Proteins; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D007633:Keratins / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
D048948:14-3-3 Proteins; D018076:DNA, Complementary; D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors; D014212:Tretinoin; D007633:Keratins; D003513:Cycloheximide; D014446:Tyrosine 3-Monooxygenase; D020928:Mitogen-Activated Protein Kinases