| Project/Area Number |
07457043
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | KOBE UNIVERSITY |
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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) |
SADA Kiyonao School of Medicine, Kobe University Research Associate, 医学部, 助手 (10273765)
YANAGI Shigeru School of Medicine, Kobe University Research Associate, 医学部, 助手 (60252003)
MINAMI Yasuhiro School of Medicine, Kobe University Associate Professor, 医学部, 助教授 (70229772)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | protein-tyrosine kinase / Syk / CD45 / Lyn / Zap-70 / cortactin / oxidative stress / DT-40 cell / 活性酸素 / ホスホリパーゼD / K562細胞 / DT40細胞 / TPA |
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| Research Abstract |
A non-receptor type protein-kinase Syk is expressed in almost all the hematopoietic cells. In this project we tried to found out the physiological role of Syk in signal transduction and also pathophysiological role od Syk. We have obtained the following results.
1)Human leukemic cell line K562 is induced to differentiate into the megakaryocytic lineage by stimulation with TPA.We found that TPA stimulation increases tyrosine phosphorylation of 80-kDa protein at an early stage of megakaryocytic differentiation and that this 80-kDa protein is identical with cortactin.
2)The roles of Syk and Lyn in radiation-induced signal transduction and radiation-induced apoptosis, we have studied using Syk-and Lyn-DT-40 cells. Syk and Lyn are involved in radiation-induced signaling, but inactivation of syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis.
3)We studied the relationship between Syk activity and cAMP.cAMP-dependent protein kinase negatively regulates the activation of Sy
… More
k in fMLP-receptor signaling in polymorphonuclear neutrophils.
4)To explore the mechanisim by which the Syk participates in B cell antigen receptor signaling, we have studied the function of various Syk mutants in B cells made Syk deficient by homologous recombination knockout. We foynd that both SH2 domains are necessary for Syk binding to tyrosine-phosphorvlated
5)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.
6)Syk is rapidely activated in B cells after hydrogen peroxide treatment (oxidative stress) or increased extracellular NaCl concentration (osmotic stress) as well as in response to B cell receptor activation. We have found that both the calcium increase and Jun-amino-teminal kinase (JNK) activity induced by oxidative stress are partly dependent on syk, whereas those induced by osmotic stress are independent of Syk.
7)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
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