Schieven G L, Kirihara J M, Burg D L, Geahlen R L, Ledbetter J A
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
J Biol Chem. 1993 Aug 5;268(22):16688-92.
We have used H2O2 as a pharmacologic agent to examine the effects of oxidizing conditions on lymphocyte signal pathways. Treatment of Ramos cells with 5-10 mM H2O2 gave rapid and strong tyrosine phosphorylation of multiple cellular proteins and activation of p72syk to levels equal to or greater than that observed upon surface Ig cross-linking. Strong Ca2+ signals that could be blocked by the tyrosine kinase inhibitor herbimycin A were also observed under these conditions. However, there was no increase in activity for the Src family kinases p56lck, p59fyn, or p56/p53lyn. Our findings that the p72syk tyrosine kinase responds to H2O2 treatment of cells suggest that this kinase is likely to contribute to cellular tyrosine phosphorylation and calcium signaling induced by oxidizing conditions. Furthermore, H2O2 may be useful as a pharmacologic agent to distinguish the effects of p72syk-related kinases from those of Src family kinases.
我们使用过氧化氢作为一种药理剂来研究氧化条件对淋巴细胞信号通路的影响。用5-10 mM过氧化氢处理拉莫斯细胞,可使多种细胞蛋白迅速且强烈地发生酪氨酸磷酸化,并使p72syk激活至与表面免疫球蛋白交联时所观察到的水平相等或更高。在这些条件下还观察到可被酪氨酸激酶抑制剂赫比霉素A阻断的强烈钙离子信号。然而,Src家族激酶p56lck、p59fyn或p56/p53lyn的活性并未增加。我们的研究结果表明,p72syk酪氨酸激酶对细胞的过氧化氢处理有反应,这表明该激酶可能有助于氧化条件诱导的细胞酪氨酸磷酸化和钙信号传导。此外,过氧化氢可能作为一种药理剂,用于区分p72syk相关激酶和Src家族激酶的作用。