Molecular and Cellular Analysis of a Leucine-rich Repeat Molecule RP105

富含亮氨酸重复分子 RP105 的分子和细胞分析

• 批准号: 09470096
• 负责人: MIYAKE Kensuke
• 金额: $ 8.32万
• 依托单位: Saga Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470096/
• 关键词: Blymphocytes; RP105; leucine-rich repeat; knockout mice; gene cloning

RP1O5 is a LRR molecule that is expressed on murine B lymphocytes. Its cross-linking with a monoclonal antibody delivers an activation signal that leads to resistance against apoptosis and massive proliferation in B cells. The following results were obtained in this term.1. Molecular cloning of MD-1, a molecule which is associated with RP1O5. A molecule that is coprecipitated with RP1O5 was purified with the anti-RP1O5 antibody and amino acid sequence was determined. With the sequence, a cDNA clone was isolated. The molecule MD-1 is a secretory molecule but binds to the extracellular LRR of RP1O5.2. The signaling pathways RP1O5 employs were examined using mice lacking signaling molecules. B cells lacking lyn, btk, Erk-specific MAP kinase, protein kinase C betaI/II, c-rel, nfkb1(p105) did not respond to the anti-RP1O5 antibody, indicating the presence of multiple signaling pathways downstream of RP1O5. There results were obtained by collaboration with Drs. S.Gerondakis (Australia) and A.Tarakhovsky (Germany).3. A monoclonal antibody against human RPIO5 was established. Human RP1O5 was expressed on B lymphocytes, associated with human MD-1, and transmits an activation signal.4. Mice lacking RP1O5 were established and now under investigation.

RP1O5 是一种在鼠 B 淋巴细胞上表达的 LRR 分子。它与单克隆抗体的交联可传递激活信号，从而抵抗 B 细胞的凋亡和大规模增殖。本学期取得了以下主要成果： 1． MD-1（一种与 RP1O5 相关的分子）的分子克隆。用抗RP1O5抗体纯化与RP1O5共沉淀的分子并确定氨基酸序列。根据该序列，分离出 cDNA 克隆。 MD-1 分子是一种分泌分子，但与 RP1O5.2 的细胞外 LRR 结合。使用缺乏信号分子的小鼠检查了 RP1O5 使用的信号通路。缺乏 lyn、btk、Erk 特异性 MAP 激酶、蛋白激酶 C betaI/II、c-rel、nfkb1(p105) 的 B 细胞对抗 RP1O5 抗体没有反应，表明 RP1O5 下游存在多种信号通路。结果是通过与博士合作获得的。 S.Gerondakis（澳大利亚）和 A.Tarakhovsky（德国）.3．建立了抗人RPIO5的单克隆抗体。人RP1O5在B淋巴细胞上表达，与人MD-1相关，并传递激活信号。4．建立了缺乏 RP1O5 的小鼠，目前正在研究中。

项目成果

Chan, V.W.F.: "The molecular mechanism of B cell Aactivation by toll-like receptor protein RP-105." J.Exp.Med.188. 93-101 (1998)

Chan, V.W.F.：“Toll 样受体蛋白 RP-105 激活 B 细胞的分子机制。”

Chan,V.W.F.: "The molecular mechanism of B cell Aactivation by toll-like receptor protein RP-105." J.Exp.Med.188. 93-101 (1998)

Chan,V.W.F.：“Toll 样受体蛋白 RP-105 激活 B 细胞的分子机制。”

Miyamoto,A.: "Establishment and characterization of pro-B cell lines from motheaten mutant mouse defective in SHP-1 protein tyrosine phosphatase." Immunol.Letters. 63. 75-82 (1998)

Miyamoto,A.：“SHP-1 蛋白酪氨酸磷酸酶缺陷的受害突变小鼠 pro-B 细胞系的建立和表征。”

Miura,Y.: "RP105 is associated with MD-1 and transmits an activation signal in human B cells." Blood. 92. 2815-2822 (1998)

Miura,Y.：“RP105 与 MD-1 相关，并在人类 B 细胞中传递激活信号。”

Mine,M.: "Peptide-binding motifs of the mixed haplotype Aβ^Z/Aα^d major histocompatibility complex class II molecule:a restriction element for auto-reactive T cells in (NZB x NZW) F1 mice." Immunology. 95. 577-584 (1998)

Mine, M.：“混合单倍型 Aβ^Z/Aα^d 主要组织相容性复合物 II 类分子的肽结合基序：(NZB x NZW) F1 小鼠中自身反应性 T 细胞的限制元件。” .577-584 (1998)