| Project/Area Number |
18370054
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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, IMCR, Professor (80252782)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,270,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2007: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2006: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | Signal transduction / Biological molecules / Protein / Brain・Neuron / Immunology / 細胞間シグナル伝達 / SHPS-1 / CD47 / 神経突起伸長 / マクロファージ機能 / 赤血球 / 貪食 |
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| Research Abstract |
SHPS-1 is a transmembrane protein whose extracellular region interacts with CD47, a ligand for SHPS-1. The cytoplasmic region of SHPS-1 binds the protein tyrosine phosphatases SHIP-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 SHIPS-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) Interaction of CD47 with SHIPS-1 cooperatively regulates neurite development and eventually it contributes to formtion of neuronal networks. (2) The cytoplasmic region as well as tyrosine phosphorylation sites in this region of SHIPS-1 appear indispensable for this inhibitory action of SHIPS-1 for macrophage phagocytosis. SHIPS-1 may regulate the attachment of phagocytosed target cells to macrophages. (3) Trans-interaction of CD47 and SHPS-1 that occurred on contact of CD47-expressing cells and SHIPS-1-expressing cells results in endocytosis of the ligand-receptor complex into either cell type (trans-endocytosis). Such endocytosis is regulated by clathrin or dynamin as well as Rae and Cdc42. (4) SHPS-1 expressed on dendritic cells is important for induction of Th17 or Th1 cells as well as activation of NKT cells.
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