Cleavage of amyloid-β precursor protein (APP) by membrane-type matrix metalloproteinases
スポンサーリンク
概要
- 論文の詳細を見る
Amyloid-β precursor protein (APP) was identified on expression cloning from a human placenta cDNA library as a gene product that modulates the activity of membrane-type matrix metalloproteinase-1 (MT1-MMP). Co-expression of MT1-MMP with APP in HEK293T cells induced cleavage and shedding of the APP ectodomain when co-expressed with APP adaptor protein Fe65. Among the MT-MMPs tested, MT3-MMP and MT5-MMP also caused efficient APP shedding. The recombinant APP protein was cleaved by MT3-MMP in vitro at the A463-M 464, N579-M580, H622-S 623, and H685-Q686 peptide bonds, which included a cleavage site within the amyloid β peptide region known to produce a C-terminal fragment. The Swedish-type mutant of APP, which produces a high level of amyloid β peptide, was more effectively cleaved by MT3-MMP than wild-type APP in both the presence and absence of Fe65; however, amyloid β peptide production was not affected by MT3-MMP expression. Expression of MT3-MMP enhanced Fe65-dependent transactivation by APP fused to the Gal4 DNA-binding and transactivation domains. These results suggest that MT1-MMP, MT3-MMP and MT5-MMP should play an important role in the regulation of APP functions in tissues including the central nervous system. © 2006 The Japanese Biochemical Society.
- 日本生化学会 = Japanese Biochemical Societyの論文
- 2006-03-01
著者
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SATO Hiroshi
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine
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Yoshizaki Tomokazu
金沢大学 医学系研究科耳鼻咽喉科
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Yoshizaki T
Department Of Otolaryngology Graduate School Of Medical Science Kanazawa University
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Yoshizaki Tomokazu
Department Of Otolaryngology School Of Medicine Kanazawa University
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Yoshizaki Tomokazu
Department Of Otolaryngology Graduate School Of Medical Science Kanazawa University
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FURUKAWA Mitsuru
Department of Otolaryngology, School of Medicine, Kanazawa University
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AHMAD Munirah
Department of Molecular Virology and Oncology, Cancer Research Institute
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TAKINO Takahisa
Department of Molecular Virology and Oncology, Cancer Research Institute
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MIYAMORI Hisashi
Department of Molecular Virology and Oncology, Cancer Research Institute
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Ahmad Munirah
Department Of Molecular Virology And Oncology Cancer Research Institute
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Sato Hiroshi
Department Of Anatomy And Developmental Neurobiology Institute Of Health Biosciences The University
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Hisashi Miyamori
Department Of Molecular Virology And Oncology Cancer Research Institute
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Sato H
Department Of Molecular Virology And Oncology Cancer Research Institute
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Takino Takahisa
Department Of Molecular Virology And Oncology Cancer Research Institute Kanazawa University
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Furukawa Mitsuru
Department Of Otolaryngology Graduate School Of Medical Science Kanazawa University
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Furukawa Mitsuru
Department Of Orthopedic Surgery Keio University School Of Medicine
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Takino Takahisa
Division of Molecular Virology and Oncology, Department of Molecular Oncology, Cancer Research Institute, Kanazawa University
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