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GPI-anchored protein-mediated cell signaling system in B-precursor cells

B 前体细胞中 GPI 锚定蛋白介导的细胞信号系统

基本信息

批准号：
15590361
负责人：
KIYOKAWA Nobutaka
金额：
$ 2.3万
依托单位：
National Research Institute for Child Health and Development
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590361/
关键词：
B-precursor cells GPI-anchored cell signaling system Lipids rafts Differentiation Pre-B cell antigen receptor Bone marrow stromal cells 糖脂質豊富膜ドメイン BLNK

项目摘要

We previously reported that the cross-linking of cluster of differentiation (CD)24 induces apoptosis in Burkitt's lymphoma cells as well as B-predursor ALL cells. CD24 is a GPI-anchored protein and this apoptosis induction is mediated by raft microdomain-mediated cell signaling system. To investigate the cell signaling mediated by GPI-anchored protein in normal B precursor cells, we developed an in vitro culture system to differentiate CD34+ cells into pro-B cells. Using this culture system, we found that the cross-linking of CD24 induced apoptosis in normal human pro-B cells.B-cell linker protein (BLNK) is a component of the B-cell receptor (BCR) signalling pathway, in which raft microdomain is deeply involved. We investigated BLNK expression in human pre-B ALL cell lines and found that one of the four cell lines tested, HPB-NULL cells, was found to lack BLNK expression, and we used these human pre-B ALL cell lines that express and do not express BLNK to investigate the intracellular signalling events following pre-BCR cross-linking. When pre-BCR was cross-linked with anti-μ heavy-chain antibodies, significant phosphorylation of intracellular molecules, including Syk, Shc, ERK MAP kinase, and AKT, and an activation of Ras were observed without regard to deficiency of BLNK expression, suggesting that BLNK is not required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signalling. By contrast, phospholipase C-gamma2 (PLC-gamma2) phosphorylation and an increase in intracellular Ca(2+) level mediated by pre-BCR cross-linking were observed only in the BLNK-expressing cells, indicating that BLNK is essential for PLC-gamma2-induced Ca(2+) influx.

我们之前报道了分化簇（cd24）的交联诱导Burkitt淋巴瘤细胞和b -前体ALL细胞凋亡。CD24是一种gpi锚定蛋白，这种凋亡诱导是由筏微结构域介导的细胞信号系统介导的。为了研究gpi锚定蛋白在正常B前体细胞中介导的细胞信号传导，我们建立了将CD34+细胞分化为前B细胞的体外培养系统。利用该培养系统，我们发现CD24交联可诱导正常人前b细胞凋亡。b细胞连接蛋白（BLNK）是b细胞受体（BCR）信号通路的一个组成部分，筏微结构域在其中发挥着重要作用。我们研究了BLNK在人b前ALL细胞系中的表达，发现四种被测试的细胞系之一HPB-NULL细胞缺乏BLNK的表达，我们使用这些表达和不表达BLNK的人b前ALL细胞系来研究pre-BCR交联后的细胞内信号事件。当bcr前体与抗μ重链抗体交联时，观察到细胞内Syk、Shc、ERK MAP激酶和AKT等分子的显著磷酸化和Ras的激活，而不考虑BLNK的表达不足，这表明BLNK不是bcr前体介导的MAP激酶和PI3激酶信号通路激活所必需的。相比之下，仅在表达BLNK的细胞中观察到磷脂酶C-gamma2 （PLC-gamma2）磷酸化和bcr前交联介导的细胞内Ca（2+）水平升高，表明BLNK对PLC-gamma2诱导的Ca（2+）内流至关重要。

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Deficiency of BLNK hampers PLC-γ2 phosphorylation and Ca2+ influx induced by the pre-B-cell receptor in human pre-B cells

DOI：
10.1111/j.1365-2567.2004.01918.x
发表时间：
2004-08-01
期刊：
IMMUNOLOGY
影响因子：
6.4
作者：
Taguchi, T;Kiyokawa, N;Fujimoto, J
通讯作者：
Fujimoto, J

Dietary bioflavonoids induce apoptosis in human leukemia cells.

膳食生物类黄酮可诱导人类白血病细胞凋亡。

DOI：
发表时间：
2005
期刊：
Leukemia Research 29・5
影响因子：
0
作者：
Jun Matsui;et al.
通讯作者：
et al.

Kenichi Mimoril, et al.: "Co-stimulatory signals distinctively affect CD20- and B-cell-antigen-receptor-mediated apoptosis in Burkitt's lymphoma/leukemia cells"Leukemia. 17・6. 1164-1174 (2003)

Kenichi Mimoril 等人：“共刺激信号显着影响伯基特淋巴瘤/白血病细胞中 CD20 和 B 细胞抗原受体介导的细胞凋亡”白血病 17·6 (2003)。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Deficiency of BLNK hampers PLC-γ2 phosphorylation and Ca^<2+> influx induced by the pre- cell receptor in human pre-B cells.

BLNK的缺乏阻碍PLC-γ2磷酸化和由人前B细胞中的前细胞受体诱导的Ca 2+ 流入。

DOI：
发表时间：
2004
期刊：
Immunology 112
影响因子：
0
作者：
Taguchi T;Kiyokawa N;Takenouchi H;Matsui J;Tang W;Nakajima H;Suzuki K;Shiozawa Y;Saito M;Katagiri YU;Takahshi T;Karasuyama H;Matsuo Y;Okita H;Fujimoto J.
通讯作者：
Fujimoto J.

Pre-BCR-mediated signal inhibits CD24-induced apoptosis in human pre-B cells

前 BCR 介导的信号抑制 CD24 诱导的人前 B 细胞凋亡