| Activation of vascular endothelial growth factor receptor 2 in a cellular model of loricrin keratoderma. | |
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MedLine Citation:
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PMID: 20236940 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Loricrin is a major constituent of the epidermal cornified cell envelope. Recently, heterozygous loricrin gene mutations have been identified in two dominantly inherited skin diseases, Vohwinkel syndrome with ichthyosis and progressive symmetric erythrokeratoderma, collectively termed loricrin keratoderma. We generated stable HaCaT cell lines that express wild-type (WT) loricrin and a mutant form found in Vohwinkel syndrome with ichthyosis, using an ecdysone-inducible promoter system. The cells expressing the mutant loricrin grew more rapidly than those expressing WT loricrin after induction for 5 days. Confocal immunofluorescence microscopy revealed that phospho-Akt occurred in the nucleolus where the mutant loricrin was also located. The level of activity of Akt kinase was about nine times higher in cells with the mutant than in those with WT loricrin. ERK1/2, the epidermal growth factor receptor, vascular endothelial growth factor (VEGF) receptor 2 and Stat3 were all phosphorylated in cells with the mutant loricrin. The docking proteins, Gab1 and c-Cbl, were also tyrosine-phosphorylated in these cells. Furthermore, chromatin immunoprecipitation assays showed that Stat3 protein bound to the VEGF promoter in cells with the mutant. Thus, this study suggests that VEGF release and the subsequent activation of VEGF receptor 2 link loricrin gene mutations to rapid cell proliferation in a cellular model of loricrin keratoderma. |
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Authors:
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Kozo Yoneda; Toshio Demitsu; Kozo Nakai; Tetsuya Moriue; Wataru Ogawa; Junsuke Igarashi; Hiroaki Kosaka; Yasuo Kubota |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-17 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-17 Completed Date: 2010-06-14 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 16184-94 Citation Subset: IM |
Affiliation:
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Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan. kyoneda@med.kagawa-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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genetics,
metabolism Cell Line, Transformed Cell Nucleus / metabolism*, pathology Cell Proliferation Epidermis / metabolism, pathology Humans Membrane Proteins / genetics, metabolism* Mitogen-Activated Protein Kinase 3 / genetics, metabolism Models, Biological* Mutation* Phosphorylation / genetics Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-cbl / genetics, metabolism STAT3 Transcription Factor / genetics, metabolism Skin Diseases, Genetic / genetics, metabolism*, pathology Vascular Endothelial Growth Factor A / genetics, metabolism Vascular Endothelial Growth Factor Receptor-2 / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/GAB1 protein, human; 0/Membrane Proteins; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 0/loricrin; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 6.3.2.-/CBL protein, human; EC 6.3.2.-/Proto-Oncogene Proteins c-cbl |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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