Action mechanisms and roles of small GTP-binding proteins

小 GTP 结合蛋白的作用机制和作用

• 批准号: 05271103
• 负责人: NOZAWA Yoshinori
• 金额: $ 111.87万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05271103/
• 关键词: Small GTP-binding protein; Vesicle transport; ADP-ribosylation; Phosphorylation; Signal transduction; 酵母

RhoA and PKC activate synergistically the membrane-bound phospholipase D (PLD) in HL60. The Toxin B and C3 toxin treatments show involvement of CDC42 in PLD activation in RBL cells. PLD cDNAs were cloned from rat (Nozawa). (2) Rhabphilin-3A binds to synaptic vesicles via anchoring protein. A newly identified homolog Doc regulates exocytosis. A target protein of Rho1 is PKC in budding yeast (Takai). (3) Target proteins of Rho are PKN and p160^<PRCK>, rhophilin, rhotekin and citron. PKN and p160^<PRCK> are activated by GTP/Rho (Narumiya). (4) Expression of RhoA and RhoGDI decreases with age in rat prostate. The 20 kDa protein (H3 histone) is ADP-ribosylated (Ishibashi). (5) A factore inbolved in Raf1 activation is identified to be 14-3-3. A MAP kinase kinase (TAK1) acts in TGF-beta signaling (Matumoto). (6) Sar1p and E112K participate in vesicle transport between endoplasm reticulum and Golgi body in yeast. SAR1 from tobacco rescues SAR1 defective mutant of yeast (Nakano). (7) A arginine-specific ADP-ribosyl transferase cloned from chiken PMN ADP-ribosylates Arg^<28> in actin (Shimoyama). (8) A novel inhibitor (CKB-1055) inhibits S6 kinase in insulin signaling and exerts insulin-like action in glycogen metabolism (Hidaka.) (9) PLA_2 inhibitor blocks fusion of Golgi bodies and vesicles leading to inhibition of secretion. Brefeldin blocks vesicle formation (Ikehara). (10) Gene expression of thymidine transports greatly repressed in DnaA defective mutant of E.coli. (Sekimizu).

RhoA和PKC协同激活HL60中的膜结合磷脂酶D(PLD)。毒素B和C3毒素处理表明，CDC42参与了RBL细胞PLD的激活。从大鼠(Nozawa)中克隆了PLD基因。(2)RhabPhilin-3A通过锚定蛋白与突触小泡结合。一种新发现的同系物DOC调节胞吐作用。Rho1的一个目的蛋白是芽殖酵母(Takai)中的PKC。(3)Rho的靶蛋白为PKN和p160^lt；PRCK&gt；PKN和p160^；PRCK；被GTP/Rho(Narumiya)激活。(4)RhoA和RhoGDI在大鼠前列腺中的表达随年龄增长而减少。20 kDa的蛋白质(H3组蛋白)是ADP核糖化的(Ishibashi)。(5)Raf1激活中的Factore被鉴定为14-3-3。一个MAP激酶(TAK1)在转化生长因子-β信号转导(Matumoto)中起作用。(6)在酵母中，Sar1p和E112K参与了囊泡在内质网和高尔基体之间的运输。烟草中的SAR1拯救了酵母的SAR1缺陷突变体(Nakano)。(7)从肌动蛋白(Shimyama)中精氨酸特异的ADP-核糖基转移酶(Arg^&lt；28&gt；(8)一种新的抑制剂(CKB-1055)在胰岛素信号转导中抑制S6激酶，并在糖原代谢中发挥胰岛素样作用(Hidaka)。(9)PLA2抑制剂阻断高尔基体和囊泡的融合，导致分泌抑制。Brefeldin阻止囊泡形成(池原)。(10)在大肠杆菌Dna A缺陷突变株中，胸腺嘧啶核苷转运基因的表达受到很大程度的抑制。(关水)。

项目成果

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Watanabe，T.：“促性腺激素-睾酮系统减少大鼠睾丸中组蛋白的单（ADP-核糖基）作用”科学。

Torii,S.: "Cytotoxicity of brefeldin A correlates with its inhibitory effect on membrane binding of COP coat proteins" J.Biol.Chem.271. 11574-11580 (1995)

Torii,S.：“布雷菲德菌素 A 的细胞毒性与其对 COP 外壳蛋白膜结合的抑制作用相关”J.Biol.Chem.271。

Sato,E.: "Eraly changes in glucose metabolism in the cerebrum of senescence accelerated mouse." Brain Res.637. 133-138 (1994)

Sato,E.：“小鼠大脑中葡萄糖代谢的早期变化加速了小鼠的衰老。”

Takano,Y.: "Role of cytoplasmic tail phosphorylation sites of platelet-activating factor receptor in agonist-induced desensitization." J.Biol.Chem.269. 22453-22458 (1994)

Takano,Y.：“血小板激活因子受体细胞质尾部磷酸化位点在激动剂诱导的脱敏中的作用。”

Okimoto,T.: "Brefeldin A protects ricin-induced cytotoxicity in human cancer KB cell line,but not in its resistant counterpart with altered Golgi structures." Cell Struct.Funct.18. 241-251 (1993)

Okimoto, T.：“布雷菲德菌素 A 可以保护人类癌症 KB 细胞系中蓖麻毒素诱导的细胞毒性，但不能保护高尔基体结构改变的耐药细胞系。”