| Project/Area Number |
14380301
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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 |
Functional biochemistry
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| Research Institution | Gunma University |
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Principal Investigator |
MATOZAKI Takashi Gunma University, Professor, 生体調節研究所, 教授 (80252782)
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| Co-Investigator(Kenkyū-buntansha) |
OHE Yoshihide Gunma University, Research Associate, 生体調節研究所, 教務員 (80125830)
KANEKO Yoriaki Gunma University, Assistant Professor, 医学部, 助手 (00334095)
OKAZAWA Hideki Gunma University, Assistant Professor, 生体調節研究所, 助手 (80334126)
KOBAYASHI Hisae Gunma University, Research Associate, 生体調節研究所, 教務員 (80234839)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥17,100,000 (Direct Cost: ¥17,100,000)
Fiscal Year 2003: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2002: ¥10,500,000 (Direct Cost: ¥10,500,000)
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| Keywords | Cell-cell signaling / Cell migration / Cell Adhesion / Ectodomain shedding / Macrophage function / SHPS-1 / CD47 / SIRPβ / 細胞内シグナル伝達 / 血小板 / 神経シナプス機能 |
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| Research Abstract |
SHPS-1 is a transmembrane protein whose extracellular region interacts with CD47 and whose cytoplasmic region binds the protein tyrosine phosphatases SHP-1 or SHP-2. CD47 is a penta-transmembrane protein, which was originally identified as a binding partner of integrin. We have recently elucidated that CD47 and SHPS-1 constitute an intercellular communication system (the CD47-SHPS-1 system), that plays important roles in the following cell functions. In this study, we investigated the physiological roles of CD47-SHPS-1 system. The results obtained are follows :
(1)The SHPS-1-SHP-2 complex positively regulated the migration of melanoma cells and other cultured cells, however engagement of SHPS-1 by CD47 prevented such regulation. Engagement of SHPS-1 by CD47 also induced the dephosphorylation of SHPS-1 and enhanced Rho activity accompanied by formation of stress fibers and adoption of a less polarized morphology. Thus, the CD47-SHPS-1 system might thus contribute to the inhibition of cel
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l migration by cell-cell contact.
(2)The phagocytosis of opsonoized red blood cells (RBCs) by peritoneal macrophages (PEMs) from mice bearing mutant SHPS-1 lacking most of cytoplasmic regions (SHPS-1-Δcyto) was markedly increased, compared wild-type PEMs. In contrast, the difference between WT and the mutant was not observed when CD47-null RBC was used as a phagocytotic target or in the presence of blocking antibodies of SHPS-1. Thus, the engagement of SHPS-1 (on macrophages) by CD47 (on RBCs) negatively regulates the phagocytosis of opsonized RBCs through a manner dependent of SHP-1.
(3)In primary cultured hippocampal neurons, SHPS-1 and CD47 were localized in a different manner ; the former predominantly on axons and the latter on dendrites, respectively. Exogenous expression of SHPS-1 and CD47 in cultured neurons also confirmed this observation.
(4)In N1E-115 neuroblastoma cells, forced expression of CD47 induced neurite extension and filopodium formation, those were further enhanced by CD47-Fc fusion protein. Such regulation involved the activation of Rac and Cdc42, and integrins containing the β3 subunit. Less
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