Journal article
Jun NH2-terminal kinase is constitutively activated in T cells transformed by the intracellular parasite Theileria parva
Proceedings of the National Academy of Sciences - PNAS, Vol.94(10), pp.5119-5124
05/13/1997
Handle:
https://hdl.handle.net/2376/115112
PMCID: PMC24641
PMID: 9144200
Abstract
When T cells become infected by the parasite
Theileria parva,
they acquire a transformed phenotype and no longer require antigen-specific stimulation or exogenous growth factors. This is accompanied by constitutive interleukin 2 (IL-2) and IL-2 receptor expression. Transformation can be reversed entirely by elimination of the parasites using the specific drug BW720c. Extracellular signal-regulated kinase and jun NH2-terminal kinase (JNK) are members of the mitogen-activated protein kinase family, which play a central role in the regulation of cellular differentiation and proliferation and also participate in the regulation of IL-2 and IL-2 receptor gene expression.
T. parva
was found to induce an unorthodox pattern of mitogen-activated protein kinase expression in infected T cells. JNK-1 and JNK-2 are constitutively active in a parasite-dependent manner, but have altered properties. In contrast, extracellular signal-regulated kinase-2 is not activated even though its activation pathway is functionally intact. Different components of the T cell receptor (TCR)-dependent signal transduction pathways also were examined. The TCRζ or CD3ɛ chains were found not to be phosphorylated and
T. parva
-transformed T cells were resistant to inhibitors that block the early steps of T cell activation. Compounds that inhibit the progression of T cells to proliferation, however, were inhibitory. Our data provide the first example, to our knowledge, for parasite-mediated JNK activation, and our findings strongly suggest that
T. parva
not only lifts the requirement for antigenic stimulation but also entirely bypasses early TCR-dependent signal transduction pathways to induce continuous proliferation.
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Details
- Title
- Jun NH2-terminal kinase is constitutively activated in T cells transformed by the intracellular parasite Theileria parva
- Creators
- Yves Galley - Institute of Animal Pathology, University of Berne, Postfach 2735, CH-3001 Berne, SwitzerlandGerry Hagens - Institute of Animal Pathology, University of Berne, Postfach 2735, CH-3001 Berne, SwitzerlandIsabel Glaser - Institute of Animal Pathology, University of Berne, Postfach 2735, CH-3001 Berne, SwitzerlandWilliam Davis - Institute of Animal Pathology, University of Berne, Postfach 2735, CH-3001 Berne, SwitzerlandMargarete Eichhorn - Institute of Animal Pathology, University of Berne, Postfach 2735, CH-3001 Berne, SwitzerlandDirk Dobbelaere - Institute of Animal Pathology, University of Berne, Postfach 2735, CH-3001 Berne, Switzerland
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.94(10), pp.5119-5124
- Academic Unit
- Veterinary Microbiology and Pathology, Department of
- Publisher
- The National Academy of Sciences of the USA
- Identifiers
- 99900548353301842
- Language
- English
- Resource Type
- Journal article