Lindvall Jessica, Islam Tahmina C
Karolinska Institutet, Clinical Research Center, Huddinge University Hospital, KFC, Novum Plan 5, SE-141 86 Huddinge, Sweden.
Biochem Biophys Res Commun. 2002 May 24;293(5):1319-26. doi: 10.1016/S0006-291X(02)00382-0.
Reactive oxygen species (ROS) or reactive oxygen intermediates (ROIs) mediate complex signaling involving multiple pathways. In this report, we demonstrate for the first time that endogenous Bruton's tyrosine kinase (Btk) and Akt can interact with each other in DT40 chicken B cells and human Nalm6 B cells and that this interaction is inducible following H2O2 stimulation. This interaction is supported by visualizing the co-localization of Btk and Akt in the perinuclear region and membrane ruffles in COS-7 cells. We have also shown the involvement of phosphatidylinositol 3-kinase (PI 3-K) and Btk in the phosphorylation of Akt following stimulation by hydrogen peroxide (H2O2). Interestingly, Akt phosphorylation was found in the presence of Btk even in the absence of oxidative stress. In addition, we have investigated the involvement of PI 3-K in the MAPKs and ERK and JNK phosphorylation, in the presence or absence of Btk. Phosphorylation of both ERK and JNK increased when the PI 3-K pathway was inhibited and both pathways were modulated positively by Btk. Taken together, based on the study of endogenous conditions, we show the novel interaction of Btk and Akt in H2O2 signaling in B cells.
活性氧（ROS）或活性氧中间体（ROIs）介导涉及多种途径的复杂信号传导。在本报告中，我们首次证明内源性布鲁顿酪氨酸激酶（Btk）和Akt在DT40鸡B细胞和人Nalm6 B细胞中可以相互作用，并且这种相互作用在H2O2刺激后可被诱导。通过观察COS-7细胞中Btk和Akt在核周区域和膜皱褶中的共定位，证实了这种相互作用。我们还表明，磷脂酰肌醇3激酶（PI 3-K）和Btk参与了过氧化氢（H2O2）刺激后Akt的磷酸化。有趣的是，即使在没有氧化应激的情况下，在有Btk存在时也发现了Akt磷酸化。此外，我们研究了在有或没有Btk的情况下，PI 3-K对丝裂原活化蛋白激酶（MAPKs）以及细胞外信号调节激酶（ERK）和应激活化蛋白激酶（JNK）磷酸化的影响。当PI 3-K途径被抑制时，ERK和JNK的磷酸化均增加，并且这两条途径均受到Btk的正向调节。综上所述，基于对内源性条件的研究，我们展示了Btk和Akt在B细胞H2O2信号传导中的新型相互作用。
