Project/Area Number |
06304050
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 総合 |
Research Field |
Structural biochemistry
|
Research Institution | GIFU UNIVERSITY |
Principal Investigator |
NOZAWA Yoshinori GIFU UNIVERSITY,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (10021362)
|
Co-Investigator(Kenkyū-buntansha) |
SIMIZU Takao TOKYO UNIVERSITY,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (80127092)
IKEZAWA Hiroo NAGOYA CITY UNIVERSITY,FACULTY OF PHARMACEUTICAL SCIENCES,PROFESSOR, 薬学部, 教授 (40080163)
INOUE Keizo TOKYO UNIVERSITY,FACULTY OF PHARMACEUTICAL SCIENCES,PROFESSOR, 薬学部, 教授 (30072937)
KANOH Hideo SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE,PROFESSOR, 教授 (70045475)
NISHIJIMA Masahiro NATIONAL INSTITUTE OF HEALTH, THE HEAD, 細胞化学部, 部長 (60072956)
|
Project Period (FY) |
1994 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥27,600,000 (Direct Cost: ¥27,600,000)
Fiscal Year 1996: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1995: ¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 1994: ¥11,400,000 (Direct Cost: ¥11,400,000)
|
Keywords | Phospholipases (A2, C,D) / Bioactive phospholipid / PAF-receptor / PAF-acetylhydrolase / GPI-anchor / PA phosphohydrolase / PIP2-binding protein / ホスホリパーゼA2,C,D / 情報変換素子 / 情報変換ホスホリパーゼ / スフィンゴ脂質 / 膜リン脂質 |
Research Abstract |
(1) PLD was synergistically activated by PKCalpha and RhoA.Rat PLD2 cDNA was cloned and mRNA levels of rPLD1a, 1b and 2 were observed to change during proliferation and differentiation (Nozawa). (2) cDNA of PAF-acetylhydrolase of guinea-pig blood plasma was isolated and the primary structure of the enzyme was determined (Nojima). (3) The CD14 was found to be the endotoxin (LPS) receptor. The signaling through LPS receptor requires PC breakdown by PLD (Nishijima). (4) The PLCdelta4 cDNA was cloned and its mRNA was expressed in the regenerating rat liver cell nuclei. A downstream molecules of Ash/Grb2 was PIP2 phosphatase (Takenawa). (5) DGKdelta and PAP2a, b were cloned. PAP2a was identified to be a Wunen homologue and PAP2b was Dri gene (Kanoh). (6) The image analysis with fluorescence microscope has shown that PS and some cytosolic factor(s) were required for the PS transfer to Golge bodies (Ohki). (7) PAF-acetylhydrolase was found to be composed of 3 subunits (alpha1, alpha2=catalytic subunits). beta subunit is the product of LIS-1 gene of Miller-Dieker syndrome (Inoue). (8) The amino acid sequences of the N-terminal and internal part of amino peptidase N were determined. GPI-anchored protein(s) was found in Sulfolobus (Ikezawa). (9) Expression of the intestinal phospholipase B-cDNA revealed that this enzyme was a novel serine esterase (Okamoto). (10) Sphingosine showed structural specific inhibition of DNA polymerase. PLA_2 purified from the chromatin fraction of rat ascitic hapatoma was 17kDa PLA_2II which was specifically localyzed (Koizumi). (11) It was demonstrated that 2 splicing variants of PAF-receptor genes were present and that leucocyte regulated by distinct promotors. Physiological functions were examined by using knock-out mice (Shimizu).
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