Analysis of signal transduction pathway in blistering mechanism of pemphigus vulgaris
| Project/Area Number |
17591165
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Gifu University |
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Principal Investigator |
AOYAMA Yumi Gifu University, Dermatology, Lecturer (90291393)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | pemphigus / keratinocvte / Desmoglein / 表皮細胞 / デスモソーム / 自己免疫性水疱症 / 細胞接着 / 医学 / 皮膚科 |
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| Research Abstract |
In this study, we examined whether AK23 mAb augments phosphorylation of Dsg3 and p38 mitogen-activating protein kinase (MAPK) in a human squamous cell line, DJM-1 cells.
AK23 mAb increased serine phosphorylation of Dsg3 and augmented activation levels of p38 MAPK. These results indicate that antibodies bind to Dsg3, but not other antigens, in the IgG fraction and can induce activation of signal transduction.
Next, we investigated that p120ctn binds to desmoglein (Dsg) 1 and 3. The tailless Dsg3 constructs △IA:AA1-641Dsg3 and △641-714Dsg3, which do not contain the intracellular anchor (IA) region, did not coprecipitate with p120cn, nor did they colocalize at the plasma membrane. Immunocytochemical analysis revealed that p120ctn does not localize to desmosomes, but co-localizes with Dsg3 at the cell surface. A biotinylation assay for Dsg3 showed that biotinylated △ 641-714Dsg3 was turned over more rapidly than wild-type Dsg3. These results indicate that the membrane proximal region (corresponding to residues 641-714) in the IA region of Dsg3 is necessary for complex formation with p120ctn, and to maintain free Dsg3 at the cell surface before it is integrated into desmosomes. In summary, we show that p120ctn is a novel interactor of the Dsg proteins, and may play a role in desmosome remodeling.
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Ten Novel Mutations of the ADARl Gene in Japanese Patients with Dyschromatosis Symmetrica Hereditaria.2007
Author(s)
N.Suzuki, T.Suzuki, K.Inagaki, S.Ito, M.Kono, T.Horikawa, S.Fujiwara, A.Ishiko, K.Matsunaga, Y.Aoyama, H.Tosaki-Ichikawa, Y.Tomita
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Journal Title
J Invest Dermatol. 127・2
Pages: 309-11
Related Report
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[Journal Article] Are desmoglein autoantibodies essential for the immunopathogenesis of pemphigus vulgaris, or just 'witnesses of disease'?2006
Author(s)
Amagai M, Ahmed AR, Kitajima Y, Bystryn JC, Milner Y, Gniadecki R, Hertl M, Pincelli C, Fridks-Hareli M, Aoyama Y, Frusic-Zlotkin M, Muller E, David M, Mimouni D, Vind-Kezunovic D, Michel B, Mahoney M, Grando S.
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Journal Title
Exp Dermatol. 15・8
Pages: 815-831
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