2003 Fiscal Year Final Research Report Summary
CROSS-TALK OF MEMBRANE LIPID SIGNALING IN CELL DEATH AND SURVIVAL
| Project/Area Number |
14370064
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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 |
Pathological medical chemistry
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| Research Institution | GIFU INTERNATIONAL INSTITUTE OF BIOTECHNOLOGY |
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Principal Investigator |
NOZAWA Yoshinori GIFU INTERNATIONAL INSTITUTE OF BIOTECHNOLOGY, DIRECTOR・CHIEF, 所長 (10021362)
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| Co-Investigator(Kenkyū-buntansha) |
BANNO Yoshiko GIFU UNIVERSITY SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (50116852)
TANAKA Masashi GIFU INTERNATIONAL INSTITUTE OF BIOTECHNOLOGY, CHIEF, 部長 (60155166)
AKAO Yukihiro GIFU INTERNATIONAL INSTITUTE OF BIOTECHNOLOGY, CHIEF, 部長 (00222505)
OHGUCHI Kenji GIFU INTERNATIONAL INSTITUTE OF BIOTECHNOLOGY, RESERCHER, 研究員 (80359257)
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| Project Period (FY) |
2002 – 2003
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| Keywords | APOPTOSIS / SURVAIVAL / Pyk2 / PHOSPHOLIPASE D / AKT / PHOSPHATIDYLINOSITOL 3-KINASE / ERK / スフィンゴシンキナーゼ |
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| Research Abstract |
We have previously proposed the notion that phospholipase D (PLD) plays an important role in the anti-apototic or survival signaling pathway. When PC12 cells were exposed to the oxidative stress (H_2O_2), the PLD activity was found to greatly increase at the early stage. It was demonstrated that the Pyk2 which acts as a scarffold and Src kinase are colsely associated with the H_2O_2-induced PLD activation. In addition, Pyk2 was found to be physically interacted with PLD as inferred by co-immunoprecipitation. Thus it was concluded that the Pyk2/Src/Akt pathway is of primary importance for the survival signaling at the early phase after the H_2O_2 stress.
On the other hand, it has been known that sphingosine kinase produces sphingosine-1-phosphate whth exerts a survival signaling by its specific receptor activation (S1Ps). Furthermore, it was shown that the sphingosine kinase was much higher in the activity and protein expression level in camptothecin (CPT)-resistant PC3 cells as compared to CPT-sensitive LNCaP cells of human prostate cancer cells. Also, we have obtained the unexpected, interesting finding that CPT treatment enhanced the SPHK activity in a time-dependent manner, but the underlying mechanism remains to be defined. This can explain at least in part the CPT-resistance of PC3 cells.
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