Studies on intracellular signal transduction through phospholipase D
| Project/Area Number |
09470032
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
NAKAMURA Shun-ichi School of Medicine, Kobe University Professor, 医学部, 教授 (40155833)
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| Co-Investigator(Kenkyū-buntansha) |
KIKKAWA Ushio Biosignal Research Center, Kobe University Professor, 教授 (40150354)
YOSHIDA Kimihisa School of Medicine, Kobe University Research Associate, 医学部, 助手 (50263372)
黒田 俊一 神戸大学, バイオシグナル研究センター, 助教授 (60263406)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | Signal transduction / Phospholipase D / G_<M2> activator / G-protein / ADP-ribosylation factor / G_<M2> gangliosidosis / G蛋白質 / 活性化因子 |
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| Research Abstract |
The hydrolysis of phosphatidylcholine by phospholipase D (PLD) is caused by a wide variety of external signals, and is now thought to generate several lipid messengers or mediators such as phosphatidic acid.
To date, some of small molecular weight G-proteins including ADP-ribosylation factor (ARF) is known to involve in the activation of PLD, although precise mechanism of the enzyme regulation remains to be elucidated. In the series of the present research, we have found that PLD is activated by a heat-stable factor found in rat kidney cytosol. The factor was purified to near homogeneity by a sequential column chromatography. The purified factor was a protein with an apparent molecular mass of 23 kDa on SDS-PAGE.The factor itself was weak to activate PLD partially purified from rat kidney. The factor, however, potently (10 fold) stimulated PLD in a synergistic manner with ARF.
Amino acid sequences of the peptides derived from the purified factor treated : with lysylendpeptidase were almost identical (87 %) with the corresponding sequences of mouse G_<M2> ganglioside activator whose deficiency is known to result in AB-variant of G_<M2> gangliosidosis. The purified factor indeed had the G_<M2> ganglioside activator activity, i.e. the enhancement of conversion of G_<M2> to G_<M3> ganglioside by beta-hexosaminidase A.
These results strongly suggest that G_<M2> ganglioside activator controls the metabolism of both phosphatidylcholine and gangliosides, and may implicate in the signaltransduction whose impairment is closely associate with G_<M2> gangliosidosis.
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Report
(3 results)
Research Products
(14 results)
