ACTIVATION OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTES-T BY PHARMACOLOGICAL INDUCTION OF PROTEIN-TYROSINE PHOSPHORYLATION
ACTIVATION OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTES-T BY PHARMACOLOGICAL INDUCTION OF PROTEIN-TYROSINE PHOSPHORYLATION
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DOI：
10.1073/pnas.89.21.10306
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发表时间：
1992-11-01
影响因子：
11.1
通讯作者：
SMYTH, MJ
中科院分区：
文献类型：
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作者：
O'SHEA, JJ;MCVICAR, DW;SMYTH, MJ
蛋白酪氨酸激酶和蛋白酪氨酸磷酸酶(PTPase)活性是T细胞抗原受体介导的信号转导所必需的。为了评估正常人T细胞酪氨酸磷酸化水平改变的功能后果，研究了钒酸盐和过氧化氢的作用。在联合作用下，这些药物诱导细胞底物酪氨酸磷酸化，细胞内游离钙升高，并诱导白细胞介素2受体(IL-2R)α链表达，但不诱导IL-2分泌。然而，抗CD28抗体联合钒酸和过氧化氢可诱导IL-2的分泌，这与诱导该基因时需要共刺激信号是一致的。在没有T细胞PTPase CD45的情况下，钒酸盐和过氧化氢的作用增强。因此，对正常T细胞酪氨酸磷酸化水平的急性药物操作与这些细胞的部分(但不是全部)激活相关；与CD28分子的扰动提供的共刺激信号相一致，启动了完整的激活程序。这些药物在剖析信号通路方面应该是有用的，这些信号通路涉及对免疫反应至关重要的基因的调节。
Protein-tyrosine kinase and protein-tyrosine phosphatase (PTPase) activities are essential for T-cell antigen receptor-mediated signaling. To assess the functional consequences of alteration of the levels of tyrosine phosphorylation in normal human T cells, the effects of vanadate and hydrogen peroxide were studied. In combination, these agents induced tyrosine phosphorylation of cellular substrates, elevated cytosolic free calcium, and induced interleukin 2 receptor (IL-2R) alpha chain expression but not IL-2 secretion. However, anti-CD28 antibody in combination with vanadate and hydrogen peroxide induced IL-2 secretion, consistent with the requirement for a costimulatory signal in the induction of this gene. The effects of vanadate and hydrogen peroxide were enhanced in the absence of the T-cell PTPase, CD45. Thus, acute pharmacologic manipulation of the level of tyrosine phosphorylation in normal T cells correlates with partial, but not full, activation of these cells; in concert with a costimulatory signal provided by perturbation of the CD28 molecule, the complete program of activation is initiated. These agents should prove useful in dissecting signaling pathways involved in the regulation of genes critical to the immune response.