Upregulation of Jun and Fos family members and permanent JNK activity lead to constitutive AP-1 activation in Theileria-transformed leukocytes

Theileria parasitises bovine leukocytes and transforms them into proliferating, metastatic tumours, where the infection resembles a leukaemia-like disease. We have studied the signal transduction pathways leading to activation of the transcription factor AP-1 in different transformed leukocytes. Parasite infection leads to an up-regulation of all members of the Jun/Fos family of proteins and surprisingly, this occurs in the absence of any detectable ERK, or p38 MAP kinase activity. In the parasitised B-sarcoma TBL3, AP-1 induction occurs in the absence of any JNK activity. In contrast, in infected macrophage and B-cell lines, AP-1 transcriptional activity is strictly associated with the parasite-induced constitutive activation of JNK and subsequent c-Jun N-terminal phosphorylation. Thus, constant AP-1 transcriptional activity involves both an upregulation in the levels of Jun and Fos proteins and constitutive JNK activation. (C) 1998 Elsevier Science B.V. All rights reserved.