| Project/Area Number |
05507001
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
NISHIZUKA Yasutomi Kobe University, School of Medicine, Professor, 医学部, 教授 (10025546)
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| Co-Investigator(Kenkyū-buntansha) |
OGITA Kouji Kobe University, School of Medicine, Research Associate, 医学部, 助手 (60204103)
NAKAMURA Shun-ichi Kobe University, School of Medicine, Associate Professor, 医学部, 助教授 (40155833)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥30,500,000 (Direct Cost: ¥30,500,000)
Fiscal Year 1994: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1993: ¥22,500,000 (Direct Cost: ¥22,500,000)
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| Keywords | Signal transduction / Protein kinase C / Phospholipase A_2 / Phospholipase D / Diacylglycerol / G-protein / tyrosine kinase |
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| Research Abstract |
Protein kinase C plays essential roles in a wide variety of cellular responses. It is accepted that phosphatidylinositol hydrolysis by phospholipase C generates diacylglycerol that is essential to protein kinase C activation. In addition, the hydrolysis of phosphatidylcholine by phospholipae D also produces diacylglycerol through the phosphatidate formation, and arachidonic acid, a product of the hydrolysis of membrane phospholipids by phospholipase A_2 reaction, also involves the signal transduction through protein kinase C.
We have shown that the primary products of the phosphatidylcholine hydrolysis by phospholipase A_2, cis-unsaturated fatty acids and 2-lysophosphatidylcholine, both appear to serve as enhancer molecules for the diacylglycerol-dependent PKC activation in cell-free enzymatic reaction and for cellular responses. Permeabilized human leukemic cell lines released various unsaturated fatty acids that is potentiated by vanadate and GTPgammaS,suggesting the involvement of tyrosine phosphorylation and GTP-binding proteins in the activation of arachidonic acid-non selective phospholipase A_2.
The results imply that several phospholipases A_2, both arachidonic acid-selective and nonselective enzymes, are coupled to receptors for their activation, thereby functioning in the transmembrane control of cellular event.
In contrast, the hydrolysis of phosphatidylcholine by phospholipase D is absolutely requires GTPgammaS and uncharacterized factors in the cytosolic fraction. PKC and tyrosine kinases both potentiates the activation of this enzyme. Dynamic change of a wide variety of lipid molecules produced by various phospholipases appears to be critical for the regulation of intracellular event.
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