| Project/Area Number |
07307003
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 総合 |
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| Research Field |
General 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) |
OKADA Masato Osaka University Insitute for protein Research Associate Professor, 蛋白質研究所, 助教授 (10177058)
NOZAWA Yoshinori Gifu University School of Medicine Professor, 医学部, 教授 (10021362)
YAMAMOTO Tadashi University of Tokyo Institute of Medical Science Professor, 医科学研究所, 教授 (40134621)
ONO Yoshitaka Kobe University Faculty of Science Professor, 理学部, 教授 (10243297)
MATOZAKI Takashi Kobe University School of Medicine Research Associate, 医学部付属病院, 助手 (80252782)
武藤 多津郎 福井医科大学, 医学部, 助手 (60190857)
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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 |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1996: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1995: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | Syk / protein-tyrosine kinase / Lyn / CD45 / DT-40 cell / SHP-2 / protein-tyrosine phosphatase / SHPS-1 / SHp-2 / チロシンホスファターゼ / パキシリン / SH-PTP2 / CSk / ZAP-70 / Trk |
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| Research Abstract |
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
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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
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