Tyrosine phosphorylation and activation of PKC and its role in celluar regulation
酪氨酸磷酸化和PKC激活及其在细胞调节中的作用
基本信息
- 批准号:10470031
- 负责人:
- 金额:$ 6.21万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:1998
- 资助国家:日本
- 起止时间:1998 至 1999
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
It has been shown that PKC, which comprises a family of ten isoforms, is activated by 1, 2-diacylglycerol produced from receptor-mediated hydrolysis of inositol phospholipids. On the other hand, the PKC isoforms have been indicated to be tyrosine phosphorylated in response to the treatment of cells with hydrogen peroxide (HィイD22ィエD2OィイD22ィエD2). Among the PKC isoforms, PKCδ is efficiently tyrosine phosphorylated and catalytically activated. In this study, phosphorylation-dependent activation of PKCδ was analyzed. Firstly, the intracellular localization of PKCδ was observed under confocal microscope by monitoring the fluorescence of the GFP-fusion protein of PKCδ. The GFP-fusion protein was translocated to the membrane by the stimuli generating 1, 2-diacylglycerol, whereas the fusion protein did not move in the HィイD22ィエD2OィイD22ィエD2-treated cells. Therefore, PKCδ was concluded to be activated by HィイD22ィエD2OィイD22ィエD2 in a manner independent of the membrane translocation induced by 1, 2-dia … More cyglycerol. It is well known that HィイD22ィエD2OィイD22ィエD2 suppresses the protein-tyrosine phosphatase reaction and thus increase tyrosine phosphorylation of various cellular proteins. Several protein-tyrosine phosphatase inhibitors, however, did not induce tyrosine phosphorylation of PKCδ, indicating that activation of protein-tyrosine kinase rather than inhibition of protein-tyrosine phosphatase is necessary for the covalent modification of PKCδ. Phosphotyrosine residues were determined by the study of a series of mutant protein of PKCδ and by the mass spectrometric analysis of the phosphopetides of PKCδ recovered from the HィイD22ィエD2OィイD22ィエD2-treated cells. Three tyrosine residues were identified, and in vitro phosphorylation of these tyrosine residues by Lck, a non-receptor type protein-tyrosine kinase, activated the enzyme. Activation of PKCδ by tyrosine phosphorylation was detected even three hours after the HィイD22ィエD2OィイD22ィエD2 treatment, and thus the active enzyme may have an important role in the long-term responses of the cells to the extracellular stimuli. Less
研究表明,PKC由10种亚型组成,可被受体介导的肌醇磷脂水解产生的1,2-二酰基甘油激活。另一方面,PKC亚型已被指示为响应于用过氧化氢处理细胞而被酪氨酸磷酸化(H β D22 β D2 O β D22 β D2)。在PKC亚型中,PKCδ被有效地酪氨酸磷酸化和催化活化。在这项研究中,PKCδ的磷酸化依赖性激活进行了分析。首先,通过共聚焦显微镜观察PKCδ在细胞内的定位。GFP-融合蛋白通过产生1,2-二酰基甘油的刺激物移位到膜上,而融合蛋白在经H2 O2处理的细胞中不移动。因此,PKCδ的激活与1,2-dia诱导的膜转位无关。 ...更多信息 聚甘油众所周知,H β D22 β D2 O β D22 β D2抑制蛋白质-酪氨酸磷酸酶反应,从而增加各种细胞蛋白质的酪氨酸磷酸化。然而,几种蛋白酪氨酸磷酸酶抑制剂并不诱导PKCδ的酪氨酸磷酸化,表明PKCδ的共价修饰需要激活蛋白酪氨酸激酶而不是抑制蛋白酪氨酸磷酸酶。通过对一系列突变蛋白的研究和对从H_(22)N_(22)D_(2)处理的细胞中回收的PKCδ磷酸化产物的质谱分析,确定了磷酸化酪氨酸残基。三个酪氨酸残基被确定,并在体外磷酸化这些酪氨酸残基的LCK,一种非受体型蛋白酪氨酸激酶,激活酶。即使在H β D22 β D2 O β D22 β D2处理后3小时,也检测到酪氨酸磷酸化激活PKCδ,因此活性酶可能在细胞对细胞外刺激的长期反应中起重要作用。少
项目成果
期刊论文数量(24)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Ohmori, S.: "Three distinct mechanisms for translocation and activation of the δ subspecies of protein kinase C"Mol. Cell. Biol.. 18・9. 5263-5271 (198)
Ohmori, S.:“蛋白激酶 C δ 亚种的三种不同机制”Mol Cell. 18・9。
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Irie,K.: "Synthesis and phorbol ester-binding studies of the individual cysteine-rich motifs of protein kinase D"Bioorg.Med.Chem.Lett.. 9・17. 2487-2490 (1999)
Irie, K.:“蛋白激酶 D 的单个富含半胱氨酸基序的合成和佛波酯结合研究”Bioorg.Med.Chem.Lett.. 9·17 (1999)。
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Takeuchi,H.: "PTB domain of insulin receptor substrate-1 binds inositol compounds." Biochem.J.334・1. 211-218 (1998)
Takeuchi, H.:“胰岛素受体底物 1 的 PTB 结构域与肌醇化合物结合。”Biochem.J.334·1(1998)。
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Takaishi, H.: "Regulation of nuclear translocation of Forkhead transcription factor AFX by protein kinase B"Proc. Natil. Acad. Sci. USA. 96・21. 11836-11841 (1999)
Takaishi,H.:“蛋白激酶 B 对叉头转录因子 AFX 的调节”,Proc Sci. 11836-11841。
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Konishi,H., Matsuzaki,H., Takaishi,H., Yamamoto,T., Fukunaga,M., Ono,Y., Kikkawa,U.: "Opposing effects of protein kinase C δ and protein kinase B α on HィイD22ィエD2OィイD22ィエD2-induced apoptosis in CHO cells"Biochem. Biophys. Res. Commun.. 264-3. 840-846 (1999
Konishi, H.、Matsuzaki, H.、Takaishi, H.、Yamamoto, T.、Fukunaga, M.、Ono, Y.、Kikkawa, U.:“蛋白激酶 C δ 和蛋白激酶 B α 对 H 的相反作用D22D2OD22D2诱导的CHO细胞凋亡“Biochem.Biophys.Res.Commun..264-3.840-846(1999
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KIKKAWA Ushio其他文献
KIKKAWA Ushio的其他文献
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{{ truncateString('KIKKAWA Ushio', 18)}}的其他基金
Regulation mechanisms of mTOR-mediated nutrient signaling by protein phosphatase PP2A
蛋白磷酸酶 PP2A 对 mTOR 介导的营养信号的调节机制
- 批准号:
20390081 - 财政年份:2008
- 资助金额:
$ 6.21万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Apoptotic dell death through lipid kinase/PKB/AFX and stress signaling pathways
通过脂质激酶/PKB/AFX和应激信号通路导致细胞凋亡
- 批准号:
14370059 - 财政年份:2002
- 资助金额:
$ 6.21万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Regulation of the activity of protein kinases depending on their functional domains
根据蛋白激酶的功能域调节其活性
- 批准号:
07557200 - 财政年份:1995
- 资助金额:
$ 6.21万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Studies on a protein-serine/threonine protein kinase family having a SH2 domain
具有SH2结构域的蛋白-丝氨酸/苏氨酸蛋白激酶家族的研究
- 批准号:
06454168 - 财政年份:1994
- 资助金额:
$ 6.21万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Properties of the delta-, epsilon-, and zeta- Subspecies of Protein Kinase C
蛋白激酶 C δ、ε 和 zeta 亚种的特性
- 批准号:
03670142 - 财政年份:1991
- 资助金额:
$ 6.21万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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Structural and functional studies of protein kinase C regulation
蛋白激酶C调节的结构和功能研究
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Protein Kinase D in oncogenic oxidative stress signaling
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Protein Kinase D in oncogenic oxidative stress signaling
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7761967 - 财政年份:2010
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7884675 - 财政年份:2010
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Development of small molecule inhibitors of protein kinase D
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Role of Protein Kinase C in Macrophage Activation
蛋白激酶 C 在巨噬细胞激活中的作用
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8051924 - 财政年份:2010
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Protein Kinase D in oncogenic oxidative stress signaling
致癌氧化应激信号传导中的蛋白激酶 D
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