Regulatory mechanisms of multi-functional sheddase
| Project/Area Number |
15570121
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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 |
Functional biochemistry
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
SAKANE Fumio Department of Biochemistry, School of Medicine, Associate Professor, 医学部, 助教授 (10183815)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Diacylglycerol kinas / Phosphatidic acid / Osmotic shock / Phorbol ester / Phosphorylation / Oligomer / SAM / Pleckstrin homology / TACE / ホルボールエスチル / ジアシルグリセロール / 腫瘍壊死因子α / トランスロケーション / プロテインキナーゼC |
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| Research Abstract |
We had ahrady obtained several lit s of evidence suggesting chat diacylglycerol kinase (DGK) 6 participates m the regulation of a multi-functional sheddase, tumor necrosis α-converning enzyme (TACE). As a next step, we by modification of DGK6 and its closely related isofoms (DGKs η and κ) in stimulated cells. DGKδ1 or its pleckstrin homology (PH) domain alone has been shown to be translocated to the plasma membranes from the cytoplasm in phorbol myristate acetate (PMA)-treated cells. In the present work we identified Ser-22 and Ser-26 within the PH domain as the PMA-and epidermal growth factor-dependent phosphorylation sites of DGKδ1. Experiments in vitro and with intact cells suggested that the conventional protein kinase C (cPKC) directly phosphorylated these Ser residues. Interestingly, the Asp-mutation, which mimics phosphoserine, at Ser-22 or Ser-26, markedly inhibited the translocation of full-length DGKδ1 and the PH domain, suggesting that the phosphorylation regulates negatively the enzyme translocation.
We identified another DGKη isoform (η2, 135 kDa) that shared the same sequence with DGKη1 except for a sterile a motif (SAM) domain added at the C-terminus. DGKη2 was shown to form through its SAM domain homo-oligomers as well as hetero-oligomers with other SAM-containing DGKs (81 and 62). Interestingly, DGKη1 and DGKη2 were rapidly translocated from the cytoplasm to endosomes in response to stress stimuli. In this case, DGKη1 l was rapidly relocated back to the cytoplasm upon removal of stress stimuli, whereas DGKη2 exhibited sustained endosomal association.
Recently, we identified a tenth member of the DGK family designated DGKκ. The new DGK isozyme has additionally 33 tandem repeats of Glu-Pro-Ala-Pro at the N-terminus. Interestingly, DGKκ, but not other type II DGKs, was specifically tyrosine-phosphorylated by Src-family kinase in H_2O_2-treated cells.
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Report
(3 results)
Research Products
(30 results)
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[Journal Article] Cloning and characterization of diacylglycerol kinase ι splice variants in rat brain2004
Author(s)
Ito T., Hozumi Y., Sakane, F., Saino-Saito, S., Kanoh, H., Aoyagi, M., Kondo, H., Goto, K.
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Journal Title
J. Biol. Chem. 279(22)
Pages: 23317-23326
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Diacylglycerol kinase γ serves as an upstream suppressor of Racl and lamellipodium formation2004
Author(s)
Tsushima, S., Kai, M., Yamada, K., Imai, S., Houkin, K., Kanoh, H., Sakane, F.
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Journal Title
J. Biol. Chem. 279(27)
Pages: 28603-28613
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Cloning and characterization of diacylglycerol kinase ι splice variants in rat brain.2004
Author(s)
Ito, T., Hozumi, Y., Sakane, F., Saino-Saito, S., Kanoh, H., Aoyagi, M., Kondo, H., Goto, K.
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Journal Title
J.Biol.Chem. 279(22)
Pages: 23317-23326
Related Report
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[Journal Article] Diacylglycerol kinase γ serves as an upstream suppressor of Rac1 and lamellipodium formation.2004
Author(s)
Tsushima, S., Kai, M., Yamada, K., Imai, S., Houkin, K., Kanoh, H., Sakane, F
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Journal Title
J.Biol.Chem. 279(27)
Pages: 28603-28613
Related Report
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[Journal Article] Gene expression, cellular localization and enzymatic activity of diacylglycerol kinase isozymes in rat ovary and placenta
Author(s)
Toya, M., Hozumi, Y., Ito, T., Takeda, M., Sakane, F., Kanoh, H., Saito, H., Hiroi, M., Kurachi, H., Kondo, H., Goto, K.
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Journal Title
Cell Tissue Res. (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Expression and localization of diacylglycerol kinase isozymes and enzymatic features in rat lung
Author(s)
Katagiri, Y., Ito, T., Saino-Saito, S., Hozumi, Y., Suwabe, A., Otake, K., Sata, M., Kondo, H., Sakane, F., Kanoh, H., Kubota, I., Goto, K.
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Journal Title
Am. J. Physiol. Lung Cell Mol. Physiol. (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Diacylglycerol kinase t regulates RasGRP3 and inhibits Rap1 signaling
Author(s)
Regier, D.S., Higbee, L, Anderson, K., Sakane, F., Prescott, S.M., Topham, M.K.
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Journal Title
Proc. Natl Acad. Sci USA (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Gene expression, cellular localization and enzymatic activity of diacylglycerol kinase isozymes in rat ovary and placenta.
Author(s)
Toya, M., Hozumi, Y., Ito, T., Takeda, M., Sakane, F., Kanoh, H., Saito, H., Hiroi, M., Kurachi, H., Kondo, H., Goto, K.
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Journal Title
Cell Tissue Res. (in press)
Related Report
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[Journal Article] Expression and localization of diacylglycerol kinase isozymes and enzymatic features in rat lung.
Author(s)
Katagiri, Y., Ito, T., Saino-Saito, S., Hozumi, Y., Suwabe, A., Otake, K., Sata, M., Kondo, H., Sakane, F., Kanoh, H., Kubota, I., Goto, K.
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Journal Title
Am.J.Physiol.Lung Cell Mol.Physiol. (in press)
Related Report
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