Study of signal transduction via an SH2 which recognizes phosphotyrosine residues of proteins
通过识别蛋白质磷酸酪氨酸残基的 SH2 进行信号转导研究
基本信息
- 批准号:07307003
- 负责人:
- 金额:$ 8.64万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (A)
- 财政年份:1995
- 资助国家:日本
- 起止时间:1995 至 1996
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
SH2 (src homology region 2) is a region which specifically recognized the phosphotyrosine residues in various proteins and is believed to be an important structure in signal transduction. A non-receptor type protein-kinase Syk is expressed in almost all the hematopoietic cells. We tried to found out the importance of 2 SH2 of Syk in signal transduction. Both SH2 domains were required for BCR-mediated Syk and phospholipase C_<gamma>2 phosphorylation, inositol 1,4,5-triphosphate release and calcium mobilization. A possible explanation for this requirement was provided by findings that recruitment of Syk to tyrosine-phosphorylated immuno-globulin a and reqiures both Syk SH2 domains.Protein tyrosine phosphatase, such as SHP-1 AND SHP-2, that contain SH2 domains play important roles in growth factor and cytokine signal transduction pathways. A protein of -115 kD that interacts with SHP-1 and SHP-2 was purified from v-src-transformed rat fibroblasts and the corresponding cDNA was cloned (SHP … More S-1). It has four YXX (L/V/I) motifs, potential tyrosine phosphorylation and SH2-domain binding sites, in its cytoplasmic region. SHP-1 may be a potential substrate for SHP-2 and may function in both growth factor-and cell adhesion-induced cell signaling.Interaction of Fyn and Zap-70 in T cells was studied. Deletion of both the SH2 and SH3 domains of Fyn resulted in the decrease of the assciation with Zap-70. Consistently, Fyn-SH2 and SH3 fused to glutathione S-transferase were able to bind to Zap-70. Thus multiple sites of Fyn and Zap-70 are involved in the association. We propose that Fyn phosphorylates and activates Zap-70 and that both kinases cooperate in TCR signaling.Tyrosine phosphorylation of paxillin was induced by nerve growth factor and epidermal growth factor and KCI.Various evidence suggested that tyrosine phosphorylation of paxillin may be involved in calcium-dependent events in neuronal and neuroendocrine cells.We have succeeded in making a CD45-deficient DT-40 cells. Using this cell lines we have found that the dephosphorylation of tyrosine residues at both autophosphorylation and negative regulatory sites is mediated by CD45 in vivo and that dephosphorylation of C-terminal tyrosine is a prerequisite for participation of Lyn in B cell receptor signaling.We have been searching the family of Syk/Zap-70 in brain and other tissues. We found novel kinases in brain and liver cells. Now we are purifying these kinases and cloning the cDNAs of these kinases. Less
SH2(SRC同源区2)是一个特异性识别磷酸酪氨酸保留在各种蛋白质中的区域,被认为是信号转导的重要结构。几乎所有造血细胞中表达了非受体型蛋白激酶SYK。我们试图发现2 SH2 SYK在信号转导中的重要性。 BCR介导的SYK和磷脂酶C_ <gamma> 2磷酸化,肌醇1,4,5-三磷酸盐释放和钙动员都需要两个SH2结构域。通过发现,将SYK募集到酪氨酸磷酸化的免疫全球蛋白A并重新汇集两个SYK SH2结构域。蛋白酪氨酸磷酸酶,例如SHP-1和SHP-2,其中包含SH2域在生长因子和细胞质信号转移中扮演重要的角色。与SHP-1和SHP-2相互作用的-115 kD的蛋白质是从V-SRC转换的大鼠成纤维细胞中纯化的,并克隆了相应的cDNA(SHP…更多S-1)。它在其细胞质区域具有四个YXX(L/V/I)基序,潜在的酪氨酸磷酸化和SH2域结合位点。 SHP-1可能是SHP-2的潜在底物,并且可以在生长因子和细胞粘合剂诱导的细胞信号传导中起作用。FYN和ZAP-70在T细胞中的相互作用是研究的。 FYN的SH2和SH3域的删除导致与ZAP-70的关联减少。一致地,融合到谷胱甘肽S-转移酶的FYN-SH2和SH3能够与ZAP-70结合。 FYN和ZAP-70的多个站点参与了协会。我们提出,FYN磷酸化并激活ZAP-70,并且两种激酶在TCR信号传导中均坐标。神经生长因子和表皮生长因子和KCI的酪氨酸磷酸化诱导了帕西林的磷酸化,而Various证据。 CD45缺陷DT-40细胞。使用这种细胞系,我们发现酪氨酸在自磷酸化和负调控位点保持抑制磷酸化是由CD45在体内介导的,并且C末端酪氨酸的去磷酸化是LYN参与B Cell接收器信号传导的先决条件。我们一直在搜索Syk/Zap-70 and其他组织。我们在大脑和肝细胞中发现了新型激酶。现在,我们正在纯化这些激酶并克隆这些激酶的cDNA。较少的
项目成果
期刊论文数量(19)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kanazawa, S., Ilic Dusko, Hashiyama, M., Okada, M., Nomura T., Aizawa, S., and Suda, T.: "Impaired development of CD4+CD8+ thymocytes by csk-"knock-in"into fyn locus" Oncogene. 13. 199-204 (1996)
Kanazawa, S.、Ilic Dusko、Hashiyama, M.、Okada, M.、Nomura T.、Aizawa, S. 和 Suda, T.:“csk-“敲入”fyn 导致 CD4 CD8 胸腺细胞发育受损
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Y.Yamanashi, T.Fukuda, H.Nishizumi, T.Inazu, K.Higashi, D.Kitamura, T.Ishida, H.Yamamura, T.Watanabe, and T.Yamamoto.: "Role of tyrosine phosphorylation of HS1 in B-cell antigen receptor-mediated signaling." J.Exp.Med.(in press).
Y.Yamanashi、T.Fukuda、H.Nishizumi、T.Inazu、K.Higashi、D.Kitamura、T.Ishida、H.Yamamura、T.Watanabe 和 T.Yamamoto.:“HS1 酪氨酸磷酸化在
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Y.Fujioka, T.Matozaki, T.Noguchi, A.Iwamatsu, T.Yamao, N.Takahashi, M.Tsuda, T.Takada, M.Kasuga.: "A novel membrance glycoprotein, SHPS-1, that binds the SH2 domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion."
Y.Fujioka、T.Matozaki、T.Noguchi、A.Iwamatsu、T.Yamao、N.Takahashi、M.Tsuda、T.Takada、M.Kasuga.:“一种新型膜糖蛋白 SHPS-1,它结合
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T,Tezuka.et.al.: "Physical and functional association of the Cbl proto-oncogene product with a Src-family protein-tyrosine kinase,p53/p56lyn,in the B-cell antigen receptor-mediated signaling." J.Exp.Med.183. 675-680 (1996)
T,Tezuka.et.al.:“Cbl 原癌基因产物与 Src 家族蛋白酪氨酸激酶 p53/p56lyn 在 B 细胞抗原受体介导的信号传导中的物理和功能关联。”
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S. Yoshimura. et. al.: "Differential translocation of phospholipase C isozymes to integrin-mediated cytoskeletal complexes in thrombin-stimulated human platelets." Biochem. Biophys. Res. Commun.225. 494-499 (1996)
S.吉村。
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YAMAMURA Hirohei其他文献
YAMAMURA Hirohei的其他文献
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{{ truncateString('YAMAMURA Hirohei', 18)}}的其他基金
Research of the novel role of Syk
赛克小说角色研究
- 批准号:
16390095 - 财政年份:2004
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Research for regulation system and new function of tyrosine kinase Syk
酪氨酸激酶Syk调控系统及新功能研究
- 批准号:
14370044 - 财政年份:2002
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Identification of apoptosis inhibitor produced by bacteria species
细菌种类产生的凋亡抑制剂的鉴定
- 批准号:
10557018 - 财政年份:1998
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
IDENTIFICATION AND CHARACTERIZATION OF Syk FAMIRY PROTEIN TYROSINE KINASE
Syk 家族蛋白酪氨酸激酶的鉴定和表征
- 批准号:
09470043 - 财政年份:1997
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular basis of pathophysiological role of Syk in blood and immumecells
Syk 在血液和免疫细胞中病理生理作用的分子基础
- 批准号:
07457043 - 财政年份:1995
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Physiological role of protein-tyrosine kinase p72^<syk>
蛋白酪氨酸激酶 p72^<syk> 的生理作用
- 批准号:
05044156 - 财政年份:1993
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for international Scientific Research
Physiological function of non-receptor type protein-tyrosine kinase p72^<syk>
非受体型蛋白酪氨酸激酶p72^<syk>的生理功能
- 批准号:
05454167 - 财政年份:1993
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Activation of cytosolic protein-tyrosine kinase and analysis of its substrate proteins
胞浆蛋白酪氨酸激酶的激活及其底物蛋白分析
- 批准号:
03454158 - 财政年份:1991
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Protein-tyrosine phosphorylation and its biological significance
蛋白质酪氨酸磷酸化及其生物学意义
- 批准号:
02304034 - 财政年份:1990
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for Co-operative Research (A)
Role of Protein-Tyrosine Kinases and Protein-Serine Kinases in Intracellular Signal Transduction
蛋白酪氨酸激酶和蛋白丝氨酸激酶在细胞内信号转导中的作用
- 批准号:
01480145 - 财政年份:1989
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
相似国自然基金
蛋白质酪氨酸激酶、蛋白质激酶C介导的磷酸化过程对肾脏钾通道的调节机制
- 批准号:30370734
- 批准年份:2003
- 资助金额:20.0 万元
- 项目类别:面上项目
非受体酪氨酸激酶c-Abl/Arg调控蛋白质降解的机理
- 批准号:30370739
- 批准年份:2003
- 资助金额:23.0 万元
- 项目类别:面上项目
相似海外基金
Novel targeted therapies for chronic myelomonocytic leukemia
慢性粒单核细胞白血病的新型靶向治疗
- 批准号:
10524992 - 财政年份:2022
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$ 8.64万 - 项目类别:
Novel targeted therapies for chronic myelomonocytic leukemia
慢性粒单核细胞白血病的新型靶向治疗
- 批准号:
10696221 - 财政年份:2022
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$ 8.64万 - 项目类别:
Molecular basis of pathophysiological role of Syk in blood and immumecells
Syk 在血液和免疫细胞中病理生理作用的分子基础
- 批准号:
07457043 - 财政年份:1995
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Physiological role of protein-tyrosine kinase p72^<syk>
蛋白酪氨酸激酶 p72^<syk> 的生理作用
- 批准号:
05044156 - 财政年份:1993
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for international Scientific Research
Action of novel non-receptor type protein-tyrosine kinase, p72^<syk>in immune cells.
新型非受体型蛋白酪氨酸激酶 p72^<syk> 在免疫细胞中的作用。
- 批准号:
05670117 - 财政年份:1993
- 资助金额:
$ 8.64万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)