Physiological roles of CD47-SHPS-1 system, an intercellular signaling, in regulation of various cellular functions

CD47-SHPS-1系统（一种细胞间信号传导）在调节各种细胞功能中的生理作用

• 批准号: 18370054
• 负责人: MATOZAKI Takashi
• 金额: $ 11.05万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18370054/
• 关键词: 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

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.

SHPS-1是一种跨膜蛋白，其胞外区与SHPS-1的配体CD 47相互作用。SHPS-1的胞质区域结合蛋白酪氨酸磷酸酶SHIP-1或SHP-2。CD 47是一种五跨膜蛋白，最初被鉴定为整合素的结合伴侣。我们最近阐明了CD 47和SHPS-1构成细胞间通讯系统（CD 47-SHPS-1系统），其在以下细胞功能中起重要作用。本研究探讨了CD 47-SHPS-1系统的生理功能。结果表明：（1）CD 47与SHIPS-1相互作用协同调控神经突起的发育，最终促进神经网络的形成。(2)SHIPS-1的细胞质区域以及该区域中的酪氨酸磷酸化位点对于SHIPS-1对巨噬细胞吞噬作用的这种抑制作用似乎是必不可少的。SHIPS-1可以调节被吞噬的靶细胞与巨噬细胞的附着。(3)在表达CD 47的细胞和表达SHIPS-1的细胞接触时发生的CD 47和SHPS-1的反式相互作用导致配体-受体复合物内吞到任一细胞类型中（反式内吞作用）。这种内吞作用受网格蛋白或发动蛋白以及Rae和Cdc 42的调节。(4)在树突状细胞上表达的SHPS-1对于诱导Th 17或Th 1细胞以及活化NKT细胞是重要的。

项目成果

Resistance to experimental autoimmune encephalomyelitis and impaired T cell priming by dendritic cells in SHPS-l mutant mice.

SHPS-1 突变小鼠中树突状细胞对实验性自身免疫性脑脊髓炎的抵抗力和 T 细胞启动受损。

• 发表时间: 2007
• 期刊: J. Immunol. 179
• 作者: Tomizawa;T.;et. al.
• 通讯作者: et. al.

Trans-endocytosis of CD47 and SHIPS-1 and its molecular Mechanism

CD47和SHIPS-1的转内吞作用及其分子机制

• 发表时间: 2007
• 作者: Ohnishi;H.;Kusakari;S.;Houketsu;K.;Murata;T.;Shinohara;M.;Murata;Y.;Okazawa;H.;and Matozaki;T.
• 通讯作者: T.

SHPS-1による皮膚免疫とToll様受容体を介したサイトカイン産生の制御

SHPS-1 通过 Toll 样受体调节皮肤免疫和细胞因子产生

• 发表时间: 2007
• 作者: 茂木精一郎;岡澤秀樹;小林久江;村田陽二;大西浩史;石川治;的崎尚
• 通讯作者: 的崎尚

Regulation by CD47-SHPS-1 system of neurite development and its molecular mechanism

CD47-SHPS-1系统对神经突发育的调控及其分子机制

• 发表时间: 2007
• 作者: 大西浩史、的崎 尚;他
• 通讯作者: 他

Regulation by CD47 of epithelial cell spreading and migration and its signal transduction

CD47对上皮细胞铺展、迁移的调控及其信号转导

• 发表时间: 2007
• 作者: Murata Y.;Shinohara M.;Morimoto N.;Okazawa H.;Ohnishi H.;and Matozaki T
• 通讯作者: and Matozaki T