2005 Fiscal Year Final Research Report Summary
Research of the novel role of Syk
| Project/Area Number |
16390095
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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, Graduate school of Medicine, Professor, 大学院・医学系研究科, 教授 (90030882)
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| Co-Investigator(Kenkyū-buntansha) |
TOHYAMA Yumi Kobe University, Graduate school of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70362770)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Cancer / Infection / Tyrosine kinase / Signal transduction |
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| Research Abstract |
(1) To investigate the role of Syk in CXCL12/CXCR4-induced signaling, wild-type Syk or its Dominant-negative form (DN-Syk) was introduced in mouse cell lines, BAF3 and 32D cells. With CXCL12 stimulation, cells became polarized with formation of a leading edge and contractile uropod at the rear end with increased motility. Overexpression of DN-Syk inhibited cell polarity due to the loss of contractile structure at the rear end. Furthermore, expression of DN-Syk suppressed betal integrin-mediated cell adhesion and CXCL12-dependent RhoA activation. These results demonstrate that Syk participates in CXCL12-induced cell polarization, which occurs in concert with cell adhesion mediated by beat1 integrin and RhoA pathway.
(2) Phagocytosis assay was performed using macrophage-like differentiated HL60 cells as phagocytes and C3bi-opsonized zymosan as a pathogen. DN-Syk or Syk-siRNA was transferred to HL60 cells. Quantitative analysis using flow cytometry and quenching assay of fluorescence-labeled-zymosan revealed that Syk is required for engulfment of C3bi-bound zymosan but not for attachment of C3bi-zymosan to complement receptor 3. To clarify the molecular mechanism how Syk affects the process of phagosome formation and its engulfment, the change of actin dynamics and the activation of RhoA were investigated. At the early stage of phagocytosis, there was a marked accumulation of actin around phagosomes, but transfer of DN-Syk or Syk-siRNA led to attenuated accumulation of actin around the nascent phagosomes. In addition, RhoA was clearly activated in HL60 cells but the activation was decreased in both mutant cells. These results indicate that Syk plays an essential role in complement-mediated phagocytosis in the process of phagosome engulfment in related to actin dynamics.
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[Journal Article] Protein-tyrosine kinase, Syk is required for pathogen engulfment in complement-mediated phagocytosis.2006
Author(s)
Shi, Y., Tohyama, Y., Kadono, T., He, J., Miah, S.M.S., Hazama, R., Tanaka, C., Tohyama, K., Yamamura, H.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Protein-tyrosine kinase, Syk, is required for CXCL12-induced polarization of B cells.2005
Author(s)
Matsusaka, S., Tohyama, Y., He, J., Shi, Y., Hazama, R., Kadono, T., Kurihara, R., Tohyama, K., Yamamura, H.
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Journal Title
Biochem.Biophys.Res.Commun. 328
Pages: 1163-1169
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lysosome is a primary organelle in B cell receptor-mediated apoptosis : an indispensable role of Syk in lysosomal function.2005
Author(s)
He, J., Tohyama, Y., Yamamoto, K., Kobayashi, M., Shi, Y., Takano, T., Noda, C., Tohyama, K., Yamamura, H.
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Journal Title
Genes Cells. 10
Pages: 23-35
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Phosphorylation and recruitment of syk by immunoreceptor tyrosine-based activation motif-based phosphorylation of tamalin.2004
Author(s)
Hirose, M., Kitano, J., Nakajima, Y.Moriyoshi, K., Yanagi, S., Yamamura, H., Muto, T., Jingami, H., Nakanishi, S.
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Journal Title
J.Biol.Chem. 279
Pages: 32308-32315
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Activation of Syk protein tyrosine kinase in response to osmotic stress requires interaction with p21-activated protein kinase Pak2γ-PAK.2004
Author(s)
Miah, S.M.S., Sada, K., Tuazon, P.T., Ling, J., Maeno, K., Kyo, S., Qu, X., Tohyama, Y., Traugh, J.A., Yamamura, H.
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Journal Title
Mol.Cell.Biol. 24
Pages: 71-83
Description
「研究成果報告書概要(欧文)」より
