Grant-in-Aid for Co-operative Research (A).
Pathological medical chemistry
|Research Institution||Nagoys City Unversity Medcal School|
SASAKI Makoto Nagoya City University Medical School, professor, 医学部, 教授 (10080003)
高橋 健治 東京大学, 理学部, 教授 (70011533)
IWANAGA Sadaaki Kyushu University, Faculty of Science, Professor, 理学部, 教授 (90029942)
市原 明 徳島大学, 酵素科学研究所, 教授 (40035374)
木南 英紀 順天堂大学, 医学部, 教授 (10035496)
KATUNUMA Nobuhiko Tokushima Bunri University. Instituta for Heslth Sciences. Professor, 健康科学研究センター, 教授 (50035375)
SUZUKI Koichi The University of Tokyo, Institute of Molecular and Cellular Biosciences, Profes, 分子細胞生物学研究所, 教授 (80011948)
OHKUBO Iwao Shiga University of Medical Science, Professor, 教授 (80152073)
|Project Fiscal Year
1991 – 1993
Completed(Fiscal Year 1993)
|Budget Amount *help
¥18,900,000 (Direct Cost : ¥18,900,000)
Fiscal Year 1993 : ¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1992 : ¥7,400,000 (Direct Cost : ¥7,400,000)
Fiscal Year 1991 : ¥8,500,000 (Direct Cost : ¥8,500,000)
|Keywords||Limited proteolysis / 94K calpain / Thrombomodulin / Hematocyte coagulation factor / Calpain activation due to inafarotion / Amyloidogenic protease / Intracellular protease transport / Antigen presentation / プロテアーゼによる情報発現 / 筋組織特異的94Kカルパイン / スロンボモジュリンの発現調節 / 血球内凝固因子 / 脳梗塞巣活性化カルパイン / アミロイドジェニックプロテアーゼ / カテプシンの細胞内選別輸送 / カテプシンの抗原提示への関与 / 筋組織特異的94Kカルバイン / カテプシン-インバリアント鎖による抗原提示の調節 / 筋組織特異的カルパイン / プロガストリンの活性化 / 心筋梗塞巣活性化カルパイン / カテプシンBの抗原阻囎への関与 / トランスゴルジ膜結合性プロセシングプロテアーゼ / プロテア-ゼによる情報発現 / プレプロタキキニン遺伝子発現調節因子 / カルパインの活性化 / カルパインペプチドの白血球遊走活性 / T細胞エイズレセプタ- / 26Sプロテアソ-ム / ニュ-カッスル病ウイルス|
This grant has facilitated the study of "Role of proteases in signal transductin and their disorders" during the last 3 years. The study was carried out under the following 4 categories.
1. Gene expression and regulation of the proteasse and the related bioactive substances.
2. Processing and transport of the precurcer proteins of the proteases and their inhibitors.
3. Induction and modulstion of signals by proteases, and the interaction of protains by the aid of proteases.
4. New functions of proteases
1. Regulatory factors for gene exprssion of preproteachykinin, a precurcer protein of substance P and substance K.were found to be 43kD and attach to DNA thrugh ths lsucine zipper domsin of the molecules. With respect to calpains. in addition to the m- and mu-calpains. novel calpain genes were found to be expressed linited in skeletal and smooth muscles. The former calpain contained 94kD large subunit and the latter two types of large subunits ; type 1 which contains calmodulin domain and ty
pe 2 without calmodulin domain.
2. Proenzymes in the rat liver were fund to be Ca^<2+>-dependently activated in the tranagogi by the membrane-bound processingprotease. Progastrin secreted from the stomsch was also shown to be activated Ca^<2+>-dependently by the endopeptidase which recognizes dibasic amino acid sequence in the C-terminus of the molecule. Coagulation system of horseshoe crab was found to reside in the hemotocytes. Factor B, factor C, agglutinin and coagulation enzyme released from large granules and tackypressin from small granules were elucidated to form the cascade reaction system. Calpain, containing 94kD large subunit found in the nucleus was interpreted to be due to the transmembrane signal peptde in the large subunit.
3. A satisfactory condition for the activation of calpain wes demonstrated to be the N-terminus cleavage of the large subunit, and ths subsequently released N-terminal peptides from the large and small subunits ware found to be chemotactic for neutrophils, monocytes and T and B lymphocytes The interaction of HIV and helper T lymphocyte was shown to be organized between the virus envglope glycoprotein pg120 and the T lymphocyte trptase and CD4 on the cell surtace.
4. Multicatalytic high molecular weight proteass (proteasome) was shown to gain the special abllity to digest ubiquitinated protein through transformation of 20s complex to 28s in the presence of ATP.In the immunological event of antigen presentation by MHC class II, cathepsin B was sohwn to paly a crucial role in the prearation of the epitope peptides. Less