Tyrosine phosphatase CD45 regulates hydrogen peroxide-induced calcium mobilization in B cells.
Tyrosine phosphatase CD45 regulates hydrogen peroxide-induced calcium mobilization in B cells.
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酪氨酸磷酸酶 CD45 调节 B 细胞中过氧化氢诱导的钙动员。
DOI：
10.1089/15230860260196281
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发表时间：
2002
影响因子：
6.6
通讯作者：
Chock,PBoon
中科院分区：
文献类型：
--
作者：
Qin,Suofu;Chock,PBoon
利用已建立的CD45缺失的DT40细胞，研究CD45在氧化应激信号转导中的作用。以对硝基苯磷酸为底物，发现CD45占总蛋白酪氨酸磷酸酶活性的近40%。过氧化氢处理后，几乎90%的磷酸酶活性迅速失活。与亲本细胞相比，CD45缺陷细胞中过氧化氢诱导的细胞蛋白酪氨酸磷酸化和c-jun氨基末端激酶活性明显增强。在CD45缺陷的DT40细胞中，过氧化氢诱导的1，4，5-三磷酸肌醇的产生和钙动员受到损害。然而，过氧化氢诱导的磷脂酶Cγ2(PLCγ2)酪氨酸磷酸化、抗磷酸酪氨酸抗体沉淀的磷脂酰肌醇3-激酶活性和Bruton‘s酪氨酸激酶的激活在CD45缺陷的DT40细胞中似乎是完整的。这表明CD45通过一种独立于PLCγ2和磷脂酰肌醇3-激酶的酪氨酸磷酸化以及激活γ‘s酪氨酸激酶的机制来介导过氧化氢激活的PLC CD2对底物的水解能力。综上所述，我们的观察表明，CD45除了具有负调节或磷酸酶活性外，还在氧化应激信号中发挥积极作用。
By taking advantage of established CD45-deficient DT40 cells, the roles of CD45 in oxidative stress signaling were investigated. Usingp-nitrophenyl phosphate as substrate, it was found that CD45 constituted nearly 40% of the total protein-tyrosine phosphatase activity. Almost 90% of the phosphatase activity was rapidly inactivated upon hydrogen peroxide treatment. Hydrogen peroxide-induced tyrosine phosphorylation of cellular proteins and c-Jun N-terminal kinase activation were markedly enhanced in CD45-deficient cells relative to that in its parental cells. In comparison, hydrogen peroxide-induced inositol 1,4,5-trisphosphate production and Ca2+mobilization were impaired in CD45-deficient DT40 cells. However, hydrogen peroxide-induced tyrosine phosphorylation of phospholipase Cγ2 (PLCγ2), phosphatidylinositol 3-kinase activity precipitated by anti-phosphotyrosine antibody, and activation of Bruton's tyrosine kinase appeared intact in CD45-deficient DT40 cells. This suggests that CD45 mediates the ability of hydrogen peroxide-activated PLCγ2 to hydrolyze its substrate via a mechanism independent of both tyrosine phosphorylation of PLCγ2 and phosphatidylinositol 3-kinase, as well as activation of Bruton's tyrosine kinase. Taken together, our observations demonstrated that, in addition to its negative regulatory or phosphatase activity, CD45 has a positive role in oxidative stress signaling.