AP-1 AND ATF-2 ARE CONSTITUTIVELY ACTIVATED VIA THE JNK PATHWAY IN THEILERIA PARVA-TRANSFORMED T-CELLS

Bovine T-cells infected by the protozoan parasite Theileria parva unde rgo 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, Lit tle 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 AT F-2 are constitutively phosphorylated in a parasite-dependent manner. Both transcription factors can be phosphorylated by jun-NH2-terminal k inase (JNK), but ATF-2 is also a substrate for p38. We determined whet her p38 is activated in T. parva-infected cells. Immunoblot analysis a nd inhibitor studies indicate that JNK, but not p38, is involved in AT F-2 phosphorylation. Based on these results and previous studies, we c onclude that parasite interference with mitogen-activated protein kina se pathways is restricted to constitutive activation of JNK. (C) 1998 Academic Press.