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 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.
Botteron
C
C
Institute of Animal Pathology, University of Berne, Switzerland.
Dobbelaere
D
D
D051698:Activating Transcription Factor 2; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases; D008213:Lymphocyte Activation; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology*; D016797:Theileria parva / Q000276:immunology* / Q000472:pathogenicity*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases