2006 Fiscal Year Final Research Report Summary
Role of Protein-tyrosine phosphatase on pathogenesis of Metabolic syndrome
| Project/Area Number |
16590876
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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 |
Metabolomics
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
MAEGAWA Hiroshi Shiga University of Medical Science, Undergraduate School of Medicine, Associate Professor, 医学部, 助教授 (00209363)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Protein Tyrosine Phosphatase1B / SREBP-1c / PP2A / Endoplasmic reticulum / CAAX signal |
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| Research Abstract |
Sterol regulatory element-binding protein-1(SREBP-1) is a key transcription factor in stimulating lipogenesis in the liver. Protein-tyrosine phosphatase 1B (PTP1B) induces SREBP-1 gene expression via protein phosphatase 2A (PP2A) activation. PTP1B is reported to be anchored on the endoplasmic reticulum (ER) via its C-terminal tail, and change in intracellular localization of PTP1B by C-terminal-truncation did not alter its inhibitory effects on insulin signaling in 3T3-L1 adipocytes. In this study, we investigated whether the change in intracellular localization of PTP1B could influence SREBP-1 gene expression. Overexpression of C-terminal truncated PTP1B(PTP1BΔCT) in rat Fao cells did not induce SREBP-1 gene expression. Furthermore, PTP1BACT failed to bind PP2A, resulting in impaired PP2A activation, whereas overexpression of wild-type PTP1B(PTP1BWT) associated with PP2A. Moreover, a membrane-targeted PTP1BACT activated PP2A with restored PP2A binding, despite the absence of its C-terminal region. Finally, overexpression of PTP1BACT into mouse primary cultured hepatocytes failed to enhance SREBP-1c mRNA, whereas membrane-targeted PTP1BACT led to enhanced SREBP-1c mRNA in hepatocytes as well as PTP1BWT. In conclusion, membrane localization of PTP1B is essential for PP2A activation, which is crucial for its enhancement of SREBP-1 gene expression.
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[Journal Article] 「研究成果報告書概要(欧文)」より2006
Author(s)
Uzu T, Kimura G Yamauchu A, Kanasaki M, Issiki K, Araki S, Sugimoto T, Nishio Y, Maegawa H, et al.
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Journal Title
J. Hypertension 24
Pages: 1627-1632
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