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
• 负责人: YAMAMURA Hirohei
• 金额: $ 4.99万
• 依托单位: KOBE UNIBERSITY (1994)福井医科大学 (1993)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454167/
• 关键词: Syk; Tyrosine kinase; PLCgamma; Interleukin2; PI 3 kinase; Lyn; Thrombin; p72syk; トロンボキサンA_2; コンカナバリンA; 活性化機構

We have reported that a porcine gene syk encoding a non-receptor type p72syk which has a unique structural character possessing the second src homology region 2 (SH2) instead of SH3 in its amino acid sequence. The expression of p72syk has been detected only in blood cells. In this project we try to find out (1) what are physiological substrates for p72syk. (2) What is the relationship between p72syk and src family kinases in signal transduction. (3) What happened in the blood cells after p72syk was knocked out. (4) Are there any diseases which p72syk activities are seriously damaged.During 2 years we obtained some good results in this project. For (1) in the platelets p72syk could phosphorylate not only PLCgamma, PI3 kinase but also GTPase activating protein. Former 2 enzymes are activated by this tyrosine-phosphorylation. Furthermore p72syk is translocated to cytoskeleton fraction during platelet activation. Recently p72syk could also phosphorylate an adaptor protein Shc. After Shc phosphorylation Grb2 is associated with Shc and after that ras pathway will be activated. (2) The src family kinases associated with B cell receptor phosphorylates the tyrosine residues of p72syk upon receptor stimulation, enhancing the activity of p72syk. (3) For the Ca2+ mobilization in the cells using syk negative and lyn negative cells p72syk mediates IP3 generation, howeverlyn regulates Ca2+ mobilization through a process independent of IP3 generation. (4) We could not meet such an exciting patients. (5) In the interleukin 2 and its receptor-signal transduction system, p72syk is quickly activated by the antibody and associated with serine rich region of beta chain. Finally p72syk is closely related to the expression of c-myc but not c-fos and c-jun.We are currently trying to clarify the role of p72syk in blood cell signal transduction system more.

我们报告说，编码非受体型P72Syk的猪基因SYK具有独特的结构特征，该特征具有第二SRC同源区2（SH2）而不是其氨基酸序列中的SH3。仅在血细胞中检测到p72syk的表达。在这个项目中，我们试图找出（1）P72Syk的生理底物是什么。 （2）信号转导中P72Syk和SRC家族激酶之间的关系是什么？ （3）P72syk被淘汰后血细胞发生了什么。 （4）是否存在P72Syk活动严重损害的任何疾病。在2年中，我们在该项目中取得了一些良好的结果。对于（1），血小板p72syk不仅可以磷酸化，不仅可以磷酸化，还可以磷酸化，PI3激酶，还可以激活蛋白GTPase激活蛋白。以前的2种酶被这种酪氨酸磷酸化激活。此外，P72Syk在血小板激活过程中被转移到细胞骨架分数。最近，P72Syk还可以磷酸化适配器蛋白SHC。 SHC磷酸化后，GRB2与SHC相关，然后将RAS途径激活。 （2）与B细胞受体有关的SRC家族激酶在受体刺激时磷酸化P72Syk的酪氨酸残基，从而增强了P72Syk的活性。 （3）对于使用SYK阴性和LYN负细胞P72Syk的CA2+动员中的Ca2+动员介导了IP3的产生，但是通过与IP3生成无关的过程调节Ca2+动员。 （4）我们无法遇到如此令人兴奋的患者。 （5）在白介素2及其受体信号转导系统中，p72syk迅速被抗体激活，并与β链的丝氨酸富含区域相关。最终，P72Syk与C-Myc的表达密切相关，但与C-Fos和C-Jun无关。我们目前正在尝试更多地阐明P72Syk在血细胞信号转导系统中的作用。

项目成果

箸本 英吉: "実験医学" 羊土社, 6 (1993)

桥本英吉：《实验医学》Yodosha，6 (1993)

Wang, X.: "Intracellular calcium dependent activation of p72^<syk> in platelets." J. Biochem.116(4). 858-861 (1994)

Wang, X.：“血小板中 p72^<syk> 的细胞内钙依赖性激活。”

Takata,M.: "Tyrosine kinase Lyn and Syk regulate the B cell receptor-coupled Ca2+ mobilization through the distinct pathway" EMBOJ.(in press).

Takata,M.：“酪氨酸激酶 Lyn 和 Syk 通过不同的途径调节 B 细胞受体偶联的 Ca2+ 动员”EMBOJ。（出版中）。

Qin, S.: "Interleukin 2 mediates p72^<syk> activation in peripheral blood lymphocytes." FEBS Lett.345. 233-236 (1994)

Qin, S.：“白细胞介素 2 介导外周血淋巴细胞中的 p72^<syk> 激活。”

Yamada, T.: "Association with B-cell antigen receptor with protein-tyrosine kinase p72^<syk> and activation by engagement of membrane IgM." Eur.J.Biochem.213 (1). 455-459 (1993)

Yamada, T.：“B 细胞抗原受体与蛋白酪氨酸激酶 p72^<syk> 的关联以及通过膜 IgM 的参与而激活。”