| Project/Area Number |
05454167
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | KOBE UNIBERSITY (1994)
福井医科大学 (1993) |
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Principal Investigator |
YAMAMURA Hirohei Kobe University School of Medicine Professor, 医学部, 教授 (90030882)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Shingo Fukui Medical School Research Associate, 医学部, 助手 (90262633)
YANAGI Shigeru Kobe University School of Medicine Research Associate, 医学部, 助手 (60252003)
INAZU Tetsuya Fukui Medical School Research Associate, 医学部, 助手 (00242587)
TANIGUCHI Takanobu Fukui Medical School Research Associate, 医学部, 助手 (60217130)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1994: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1993: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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