2003 Fiscal Year Final Research Report Summary
Research for regulation system and new function of tyrosine kinase Syk
| Project/Area Number |
14370044
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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 |
General medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
YAMAMURA Hirohei Kobe University, Dept of genome sciences, Prof., 大学院・医学系研究科, 教授 (90030882)
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| Co-Investigator(Kenkyū-buntansha) |
TOHYAMA Yumi Kobe University, Dept of genome sciences, Res.Assoc., 大学院・医学系研究科, 助手 (70362770)
SADA Kiyonao Kobe University, Dept of genome sciences, Assist.Prof., 大学院・医学系研究科, 講師 (10273765)
YANAGI Shigeru Kobe University, Dept of genome sciences, Assoc.Prof., 大学院・医学系研究科, 助教授 (60252003)
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| Project Period (FY) |
2002 – 2003
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| Keywords | protein-tyrosine kinase / Syk / Pak2 / Cbl / ubiquitination / 3BP2 / phagocytosis / lysosomes |
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| Research Abstract |
1) Treatment of cells with sorbitol to induce hyperosmolarity results in the translocation of Pak2 and Syk to the region surrounding the nucleus and in dramatic enhancement of their association. Cotransfection of Pak2 and Syk leads to the activation of JNK under hyperosmotic conditions. Pak2 short interfering RNA suppresses sorbitol-mediated activation of endogenous Syk and JNK, thus identifying a novel pathway for JNK activation by Cdc42.
2) Aggregation of the high affinity IgE receptor (Fc varepsilon RI) induces the rapid ubiquitination of Lyn in rat basophilic leukaemia RBL-2H3 cells. Treatment of cells with a proteasome inhibitor enhances the ubiquitination of Lyn. Co-transfection study shows that both c-Cbl and Cbl-b could induce the ubiquitination of activated Lyn in COS cells. Over-expression of membrane-anchored form of c-Cbl inhibits the Fc varepsilon RI-mediated degranulation and cytokine gene production in RBL-2H3 cells by the down-regulation of the kinase activity of Lyn through the enhanced ubiquitination. Furthermore Cbl-b is a negative regulator of both Lyn-Syk-LAT and Gab2 mediated complementary signaling pathways in FcepsilonRI-mediated mast cell activation.
3) Using the transient expression system in COS-7 cells, 3BP2 was predominantly phosphorylated on Y174, Y183, and Y446 when it was coexpressed with Syk. An in vitro binding study revealed that phosphorylation of Y446 by Syk was likely to create a binding site for the Lyn-SH2 domain in RBL-2H3 cells. In addition, proline-rich region of 3BP2 bound to the Lyn-SH3 domain. Overexpression of 3BP2 in RBL-2H3 cells resulted in an enhancement of Lyn autophosphorylation. Thus the adaptor protein 3BP2 is a potential regulator of Lyn as a ligand of its SH3/SH2 domains in EcepsilonRI-mediated signaling in mast cells.
4) As the role of Syk related to phagocytosis, we showed that Syk is essential for the endosomal fusion to lysosomes in the crosslinking-induced-endocytosis.
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Research Products
(14 results)
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[Publications] Gao, S., Takano, T., Sada, K., He, J., Noda, C., Hori-Tamura, N., Tomoda, A., Yamamura, H.: "A novel phenoxazine derivative suppresses surface IgM expression in DT4OB cell line."Brit.J.Pharmacol.. 137(6). 749-755 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sada, K., Miah.S.M., Maeno, K., Kyo, S., Qu, X., Yamamura, H.: "Regulation of FcεRI-mediated degranulation by an adaptor protein 3BP2 in rat basophilic leukemia RBL-2H3 cells."Blood. 100(6). 2138-2144 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Maeno, K., Sada, K., Kyo, S., Miah, S.M., Kawauchi-Kamata, K., Qu, X., Shi, Y, Yamamura, H.: "Adaptor protein 3BP2 is a potential ligand of Src homology 2 and 3 domains of Lyn protein-tyrosine kinase."J.Biol.Chem.. 278(27). 24912-24920 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Kyo, S., Sada, K., Qu, X., Maeno, K., Miah, S.M., Kawauchi-Kamata, K., Yamamura, H.: "Negative regulation of Lyn protein-tyrosine kinase by c-Cbl ubiquitin-protein ligase in FcεRI-mediated mast cell activation."Genes Cells. 8(10). 825-836 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Qu, X., Sada, K., Kyo, S., Maeno, K., Miah, S.M., Yamamura, H.: "Negative regulation of FcεRI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b."Blood. 103(5). 1779-1786 (2004)
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「研究成果報告書概要(欧文)」より
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[Publications] Miah, S.M., Sada, K., Tuazon, T., Ling, J., Maeno, K., Kyo, S., Qu, X., Tohyama, Y, Traugh, J.A., Yamamura H.: "Activation of Syk protein-tyrosine kinase in response to osmotic stress requires the interaction with p21-activated protein kinase Pak2/γ-PAK."Mol.Cell.Biol.. 24(1). 71-83 (2004)
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「研究成果報告書概要(欧文)」より
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[Publications] Enoki, E., Sada, K., Qu, X., Kyo, S., Miah, S.M., Hatani, T., Tomoda, A., Yamamura, H.: "The phenoxazine derivative Phx-1 suppresses IgE-mediated degranulation in rat basophilic leukemia RBL-2H3 cells."J.Pharmacol.Sci.. 94(3). 329-333 (2004)
Description
「研究成果報告書概要(欧文)」より
