Botteron C, Dobbelaere D
Institute of Animal Pathology, University of Berne, Switzerland.
Biochem Biophys Res Commun. 1998 May 19;246(2):418-21. doi: 10.1006/bbrc.1998.8635.
Bovine T-cells infected by the protozoan parasite Theileria parva undergo lymphoblastoid transformation, and proliferate in an uncontrolled manner. While it has been established that the transcription factor NF-kappa B is constitutively activated in T. parva-infected T-cells, little is known about other transcription factors such as AP-1 and ATF-2. We demonstrated increased binding activity to the AP-1 and CREB/ATF-2 consensus binding sites and show that the AP-1 complex is composed of c-Jun, JunD, c-Fos, and ATF-2. The transcription factors c-Jun and ATF-2 are constitutively phosphorylated in a parasite-dependent manner. Both transcription factors can be phosphorylated by jun-NH2-terminal kinase (JNK), but ATF-2 is also a substrate for p38. We determined whether p38 is activated in T. parva-infected cells. Immunoblot analysis and inhibitor studies indicate that JNK, but not p38, is involved in ATF-2 phosphorylation. Based on these results and previous studies, we conclude that parasite interference with mitogen-activated protein kinase pathways is restricted to constitutive activation of JNK.
被原生动物寄生虫小泰勒虫感染的牛T细胞会经历淋巴母细胞样转化，并以不受控制的方式增殖。虽然已经确定转录因子核因子κB在小泰勒虫感染的T细胞中持续激活，但对于其他转录因子如活化蛋白-1（AP-1）和活化转录因子2（ATF-2）知之甚少。我们证明了对AP-1和CREB/ATF-2共有结合位点的结合活性增加，并表明AP-1复合物由c-Jun、JunD、c-Fos和ATF-2组成。转录因子c-Jun和ATF-2以寄生虫依赖的方式持续磷酸化。这两种转录因子都可以被Jun氨基末端激酶（JNK）磷酸化，但ATF-2也是p38的底物。我们确定了p38在小泰勒虫感染的细胞中是否被激活。免疫印迹分析和抑制剂研究表明，JNK而非p38参与了ATF-2的磷酸化。基于这些结果和先前的研究，我们得出结论，寄生虫对丝裂原活化蛋白激酶途径的干扰仅限于JNK的持续激活。
