Negative signaling in B cells mediated by SHP-1

SHP-1 介导的 B 细胞负信号传导

• 批准号: 14570287
• 负责人: FUSAKI Noemi
• 金额: $ 2.24万
• 依托单位: Tokyo University of Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-14570287/
• 关键词: SHP-1; BCR; Actin; CD72; ITIM; Lipid Raft; Tyrosine phosphatase; tyrosine phosphorylation; lipid raft

To elucidate the role of tyrosme-phosphatase SUP-1 in B cells, we have investigated new substrates of SUP-1, and identified actin and myosm as the substrates.These two proteins contained ITIMs and were tyrosine-phosphorylated after BCR stimulation.Hyper-phosphorylation of actin resulted in sustained actin polymerization in B cells expressing C/S SUP-1 mutant, suggesting that SUP-1 plays a pivotal role in reorganization of cytoskeletal architecture inducing acm dephophorylation.Furthermore, we also analyzed negative function of CD72, we had previously identified as a substrate of SUP-1.We generated ITIM mutants of CD72 and introduced into DT-4O cells that lacked chick homolog of CD72, CuB1 and ChB1r.N-ITIM mutant-expressing cells showed increased phophorylation of CD72 and NF-kB activation after BCR stimulation, indicating that lack of SUP-1 binding resulted in hyper-phosphorylation of Grb2-binding site and activation of NF-kB. We also found that CD72 was existed on lipid raft and palniitoylation of CD72 was important to its localization.

为了阐明酪氨酸磷酸酶β 1在B细胞中的作用，我们研究了β 1的新底物，并鉴定了肌动蛋白和肌球蛋白作为底物。这两种蛋白含有ITIM，在BCR刺激后被酪氨酸磷酸化。在表达C/S β 1突变体的B细胞中，肌动蛋白的过度磷酸化导致肌动蛋白持续聚合，提示CD 72 -1在acm脱磷酸化诱导的细胞骨架结构重组中起着关键作用。此外，我们还分析了CD 72的负功能，我们产生了CD 72的ITIM突变体并将其导入缺乏CD 72的鸡同源物的DT-40细胞中，CuB 1和ChB 1 r.N-ITIM突变体表达细胞在BCR刺激后显示出CD 72磷酸化和NF-κ B活化的增加，这表明缺乏BCR-1结合导致Grb 2结合位点的过度磷酸化和NF-κ B的活化。同时发现CD 72存在于脂筏上，其棕榈酰化对其定位有重要作用。

项目成果

Baba, T., Fusaki, N.: "Actin is an in vivo substrate of the protein tyrosine phosphatase (SHP-1) after mIgM cross-linking"Journal of Immunology. (in press). (2003)

Baba, T., Fusaki, N.：“肌动蛋白是 mIgM 交联后蛋白酪氨酸磷酸酶 (SHP-1) 的体内底物”《免疫学杂志》。

Baba T, Fusaki N, Shinya N, Iwamatsu A, Hozumi N.: "Myosin is an in vivo substrate of the protein tyrosine phosphatase(SHP-1)after mIgM cross-linking."Biochem Biophys Res Commun.. 304(1). 67-72 (2003)

Baba T、Fusaki N、Shinya N、Iwamatsu A、Hozumi N.：“肌球蛋白是 mIgM 交联后蛋白酪氨酸磷酸酶 (SHP-1) 的体内底物。”Biochem Biophys Res Commun.. 304(1)

Baba, T., Fusaki, N.: "Actin tyrosine dephosphorylation by the Src homology 2-containing protein tyrosine phosphatase is essential for actin depolymerization after membrane IgM cross-linking"Journal of Immunology. 170(7). 3762-3768 (2003)

Baba, T., Fusaki, N.：“含有 Src 同源性 2 的蛋白酪氨酸磷酸酶对肌动蛋白酪氨酸去磷酸化对于膜 IgM 交联后肌动蛋白解聚至关重要”《免疫学杂志》。

房木 ノエミ: "臨床免疫41(3)"科学評論社. 257-262 (2004)

Noemi Fusaki：“临床免疫学 41(3)” Kagaku Hyoronsha 257-262 (2004)。

Baba, T., Fusaki, N.: "Myosin is an in vivo substrate of the protein tyrosine phosphatase (SHP-1) after mIgM cross-linking."Biochem Biophys Res Commun.. 304(1). 67-72 (2003)

Baba, T., Fusaki, N.：“肌球蛋白是 mIgM 交联后蛋白质酪氨酸磷酸酶 (SHP-1) 的体内底物。”Biochem Biophys Res Commun. 304(1)。