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The Signal Transduction Mechanisms of a GPI-anchored Complement Regulatory Protein, CD59.

GPI 锚定补体调节蛋白 CD59 的信号转导机制。

基本信息

批准号：
08672654
负责人：
HATANAKA Michiyo
金额：
$ 1.47万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672654/
关键词：
GPI-anchored protein complement regulatory protein CD59 dimer formation signal transduction C9 peptide intracellular Ca^<2+> concentration トランスジューサ-分子 Caveolin 細胞増殖架橋試薬

项目摘要

Many proteins are attached to the cell membranes via glycosyl phosphatidyl anchor rather than by a transmembrane anchor and have no direct contact with the inside of the cells. Despite this, cross-linking of GPI-anchored proteins with antibodies causes activation of T cells and neutrophils. The activation is likely to be mediated through Src kinases. It has been suggested that interaction of the GPI-anchored molecule with kinases requires a transmembrane-transducing element, the identity of which remained controversial.In this study, we focused on a GPI-anchored complement regulatory protein, CD59, as a model, to elucidate the GPI-anchored protein mediating signaling. We identified CD59 associating protein by cross-linking of surface proteins with chemical cross-linker followed by Western blotting with anti-CD59 antibody. The Cd59-associating molecules were estimated to be 13-18 kDa in size. Two-dimensional electrophoresis of the cross-linked products revealed no trace of molecules other than CD59. The cross-linked products showed the same N-terminal sequences as CD59 and a strikingly similar amino acid composition to that of CD59. Thus, most likely, the cross-linked products are CD59 dimers. The finding that CD59 localized on outer membranes is all in the form of dimers suggests the importance of dimerization for CD59 functioning.

许多蛋白质通过糖基磷脂酰锚而不是通过跨膜锚附着于细胞膜，并且与细胞内部没有直接接触。尽管如此，GPI锚定蛋白与抗体的交联引起T细胞和嗜中性粒细胞的活化。这种激活可能通过Src激酶介导。本研究以GPI锚定的补体调节蛋白CD 59为模型，探讨GPI锚定蛋白介导的信号转导机制。我们通过化学交联剂交联表面蛋白，然后用抗CD 59抗体进行Western印迹来鉴定CD 59相关蛋白。Cd 59-缔合分子的大小估计为13-18 kDa。交联产物的二维电泳显示除了CD 59之外没有分子的痕迹。交联产物显示与CD 59相同的N-末端序列和与CD 59惊人相似的氨基酸组成。因此，最有可能的是，交联产物是CD 59二聚体。CD 59定位于外膜上均为二聚体形式的发现表明二聚化对于CD 59功能的重要性。