Research for physiological roles of the CD47-SHPS-1 system.

CD47-SHPS-1系统的生理作用研究。

• 批准号: 14380301
• 负责人: MATOZAKI Takashi
• 金额: $ 10.94万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14380301/
• 关键词: 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

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 … More 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

SHPS-1是一种跨膜蛋白，其细胞外区域与CD 47相互作用，其细胞质区域结合蛋白酪氨酸磷酸酶SHP-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，CD 47和SHPS-1构成细胞间通讯系统（CD 47-SHPS-1系统），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）SHPS-1-SHP-2复合物对黑色素瘤细胞和其他培养细胞的迁移具有正调节作用，但SHPS-1与CD 47的结合阻止了这种调节作用。CD 47与SHPS-1的结合也诱导了SHPS-1的去磷酸化和Rho活性的增强，伴随着应力纤维的形成和极化程度较低的形态学的采用。因此，CD 47-SHPS-1系统可能有助于抑制细胞凋亡。 ...更多信息 l通过细胞-细胞接触的迁移。（2）SHPS-1-Δcyto突变体小鼠腹腔巨噬细胞（PEMs）对调理红细胞（RBC）的吞噬作用明显高于野生型PEMs。相反，当CD 47-null RBC用作吞噬靶或在SHPS-1的阻断抗体存在下时，未观察到WT和突变体之间的差异。因此，CD 47（在RBC上）与SHPS-1（在巨噬细胞上）的接合通过依赖于SHP-1的方式负调节调理RBC的吞噬作用。(3)In原代培养的海马神经元、SHPS-1和CD 47以不同的方式定位;前者主要位于轴突上，后者分别位于树突上。SHPS-1和CD 47在培养神经元中的外源性表达也证实了这一观察结果。(4)In N1 E-115神经母细胞瘤细胞中，CD 47的强制表达诱导神经突起延伸和丝状伪足形成，这些被CD 47-Fc融合蛋白进一步增强。这种调节涉及Rac和Cdc 42以及含有β3亚基的整合素的激活。少

项目成果

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Hayashi, A. 等人：“SIRPβ 吞噬作用的正向调节及其在巨噬细胞中的信号传导机制”。J.Biol.Chem.（印刷中）。

Sato, R., et al.: "Regulation of multiple functions of SHPS-1, a transmembrane glycoprotein, by its cytoplasmic region."Biochem.Biophys.Res.Commun.. 309巻・3号. 584-590 (2003)

Sato, R., 等人：“SHPS-1（一种跨膜糖蛋白）的细胞质区域对多种功能的调节。”Biochem.Biophys.Res.Commun.. 第 309 卷，第 3. 584-590 期（ 2003）

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Ito, T., 等人：“SAP-1（一种跨膜型蛋白酪氨酸磷酸酶）与酪氨酸激酶 Lck 的相互作用：在 T 细胞功能调节中的作用。”J.Biol.Chem.. 第 278 卷， 37第34854-34863号（2003）

Takada, T., et al.: "Induction of apoptosis by stomach cancer-associated protein tyrosine phosphatase-1 (SAP-1)"J. Biol. Chem.. 277巻・37号. 34359-34366 (2002)

Takada, T., et al.:“胃癌相关蛋白酪氨酸磷酸酶-1 (SAP-1)诱导细胞凋亡”J. Biol. 277, No. 37. 34359-34366 (2002)

Murai-Takabe, R., et al.: "Ubiquitination-mediated regulation of biosynthesis of the adhesion receptor SHPS-1 in response to endoplasmic reticulum stress."J.Biol.Chem.. 279巻・12号. 11616-11625 (2004)

Murai-Takabe, R. 等人：“泛素化介导的粘附受体 SHPS-1 响应内质网应激的生物合成调节”，J.Biol.Chem，第 279 卷，第 11616-11625 期。 (2004)