2004 Fiscal Year Final Research Report Summary
Molecular mechanism of IRS-1 degradation by PLGγ and PP2C
| Project/Area Number |
14571089
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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 |
EGAWA Katsuya Shiga University of Medical Science, Department of Medicine, Assistant professor, 医学部, 助手 (10335169)
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| Project Period (FY) |
2002 – 2004
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| Keywords | PLCg / PP2C / IRS-1 degradation / adenovirus |
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| Research Abstract |
We found that U73122,which was phospholioase C(PLC) inhibitor, blocked insulin-induced glucose uptake in 3T3-L1 adipocytes. Moreover, overexpression of PLCγ stimulated glucose uptake without insulin stimulation in a dose dependent manner. Overexpression of PLCγ did not affect phosphorylation of Akt, but enhanced phosphorylation of atypical PKC. Thus, it suggests that PLCγ stimulates gluxoce uptake through activation of atypical PKC.
Overexpression of protein phosphatase 2C(PP2C) caused dephosphorylation of serine residue of p85 of PI 3-kinase, and positively regulated insulin signaling. On the other hand, overexpression of PP2C accelerated insulin-stimulated IRS-1 degradation. When we suppressed PP2C protein expression by sRNA interference method, insulin-induced IRS-1 degradation was inhibited. Moreover, PP2C-induced IRS-1 degradation was completely inhibited by lactasistine treatment, which was proteasome inhibitor. PI 3-kinase inhibitor, wortmannin, also suppressed it, partially. Taken together, PP2C has both positive and negative effects on insulin signaling through PI 3-kinase pathway.
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Research Products
(14 results)
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[Journal Article] Protein-tyrosine phosphatase 1B as new activator for hepatic lipogenesis via sterol regulatory element-binding protein-1 gene expression.2003
Author(s)
Shimizu S, Ugi S, Maegawa H, Egawa K, Nishio Y, Yoshizaki T, Shi K, Nagai Y, Morino K, Nemoto K, Nakamura T, Bryer-Ash M, Kashiwagi A.
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Journal Title
J Biol Chem 278
Pages: 43095-43101
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Membrane localization of 3-phosphoinositide-dependent protein kinase-1 stimulates activities of Akt and Atypical PKC, but does not stimulate glucose transport and glycogen synthesis in 3T3-L1 adipocytes.2002
Author(s)
Egawa K, Maegawa H, Shi K, Nakamura T, Obata T, Yoshizaki T, Morino K, Shimizu S, Nishio Y, Suzuki E, Kashiwagi A.
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Journal Title
J Biol Chem 277
Pages: 38863-38869
Description
「研究成果報告書概要(欧文)」より
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