Activation of Helicobacter pylori VacA Toxin by Alkaline or Acid Conditions Increases Its Binding to a 250-kDa Receptor Protein-tyrosine Phosphatase β*

Activation of Helicobacter pylori VacA Toxin by Alkaline or Acid Conditions Increases Its Binding to a 250-kDa Receptor Protein-tyrosine Phosphatase β*
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碱性或酸性条件激活幽门螺杆菌 VacA 毒素会增加其与 250 kDa 受体蛋白酪氨酸磷酸酶 β* 的结合

DOI:
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发表时间:
1999
影响因子:
4.8
通讯作者:
T. Hirayama
T. Hirayama
中科院分区:
生物学2区
文献类型:
--
作者:
K. Yahiro;T. Niidome;M. Kimura;T. Hatakeyama;H. Aoyagi;H. Kurazono;K. Imagawa;A. Wada;J. Moss;T. Hirayama

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幽门螺杆菌,一种革兰氏阴性胃细菌,分泌VacA,一种细胞毒素,导致易感细胞的空泡变性。速度沉降分析表明,在碱性pH下处理VacA会导致VacA低聚物的分解,这是之前对酸处理VacA的观察结果。间接免疫荧光和流式细胞术显示,暴露于酸或碱中会增加VacA与AZ-521细胞的结合。此外,先前暴露于酸或碱处理的VacA的AZ-521细胞中含有抗VacA多克隆抗体的免疫沉淀具有250 kda的糖蛋白,其中含有半乳糖-β(1-3)- n -乙酰半乳糖胺和半乳糖-β(1-4)- n -乙酰氨基葡萄糖胺。p250经花生凝集素亲和柱和Superose 6柱层析纯化,分别含有YRQQRKLVEEIGWSYT和LIIQDHILEATQDDY的n端和内部氨基酸序列。这些序列与受体蛋白酪氨酸磷酸酶(RPTPβ/PTPζ)的序列相同;p250与抗人RPTPβ单克隆抗体反应一致。用抗人RPTPβ抗体免疫沉淀之前与VacA或热灭活的VacA孵育的溶解膜制剂表明,RPTPβ结合天然的,但不变性的VacA。酸性和碱性处理与VacA的激活和细胞表面RPTPβ结合增加有关。
Helicobacter pylori, a Gram-negative gastric bacterium, secretes VacA, a cytotoxin that causes vacuolar degeneration of susceptible cells. Velocity sedimentation analysis showed that treatment of VacA at alkaline pH led to disassembly of VacA oligomers, an observation reported previously for acid-treated VacA. Exposure of VacA to acid or alkali increased its binding to AZ-521 cells, as shown by indirect immunofluorescence and flow cytometry. Moreover, immunoprecipitates with polyclonal antibodies against VacA from AZ-521 cells previously exposed to acid- or alkali-treated VacA had a 250-kDa glycoprotein containing galactose-β(1–3)-N-acetylgalactosamine and galactose-β(1–4)-N-acetylglucosamine. p250, purified by chromatography on peanut agglutinin affinity and Superose 6 columns, contained N-terminal and internal amino acid sequences of YRQQRKLVEEIGWSYT and LIIQDHILEATQDDY, respectively. These sequences are identical to those of a receptor protein-tyrosine phosphatase (RPTPβ/PTPζ); in agreement, p250 reacted with anti-human RPTPβ monoclonal antibody. Immunoprecipitation with anti-human RPTPβ antibody of solubilized membrane preparations previously incubated with VacA or heat-inactivated VacA demonstrated that RPTPβ bound native, but not denatured, VacA. Acidic and alkaline treatments were associated with activation of VacA and increased binding to the cell surface RPTPβ.
DOI: --
发表时间: 1994-04
期刊: The Journal of biological chemistry
影响因子: --
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T. Cover;M. Tummuru;P. Cao;S. Thompson;M. Blaser
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DOI: 10.1016/s0021-9258(19)75677-4
发表时间: 1987-02
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DOI: 10.1093/ajcp/86.5.575
发表时间: 1986-11
影响因子: 3.5
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通讯作者: Xiao Geng Chen;P. Correa;J. Offerhaus;Elsie Rodriguez;F. Janney;E. Hoffmann;James G. Fox;F. Hunter;S. Diavolitsis
幽门螺杆菌培养上清液干扰人胃 KATO III 细胞中表皮生长因子激活的信号转导。
DOI: --
发表时间: 1998
期刊: The American journal of pathology
影响因子: --
作者:
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通讯作者: Tarnawski,AS