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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-02-0456. This Article Full Text (PDF) All Versions of this Article: 2002-02-0456v1 101/5/1874    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Baumgartner, M. Articles by Langsley, G. Search for Related Content PubMed PubMed Citation Articles by Baumgartner, M. Articles by Langsley, G. Social Bookmarking                   What's this? Submitted February 12, 2002 Accepted September 17, 2002 Constitutive exclusion of Csk from Hck-positive membrane microdomains permits Src kinase-dependent proliferation of Theileria-transformed B-lymphocytes Martin Baumgartner, Pavla Angelisova, Niclas Setterblad, Nuala Mooney, Dirk Werling, Vaclav Horejsi, and Gordon Langsley* Department of Parasitology, Institut Pasteur, Paris, France, France Institute of Moleuclar Genetics, Prague, Czech Republic Immunogenetic Humaine, INSERM, Unite 396, Paris, France Faculty of Veterinary Medicine, Institute of Veterinary Virology, Bern, Switzerland Department of Stomatology, University of California, San Francisco, San Francisco, CA, USA * Corresponding author; email: langsley{at}pasteur.fr. Infection of bovine T cells and B cells with the intracellular protozoan parasite Theileria parva induces a transformed phenotype with characteristics comparable to leukaemic cells. The transformed phenotype reverts upon drug-induced parasite death and the cured lymphocytes acquire a resting phenotype and eventually die by apoptosis if not further stimulated. Here, we show that both lymphocyte proliferation and activation of the transcription factor AP-1 are mediated by Src-family protein tyrosine kinases (PTKs) in a parasite-dependent fashion. Src-family PTKs are known to be present in glycolipid-enriched microdomains (GEMs), also called lipid rafts, and to be negatively regulated by PTK Csk complexed to tyrosine-phosphorylated transmembrane adapter protein PAG (phosphoprotein associated with GEMs) called also Cbp (Csk-binding protein). We therefore purified GEMs from proliferating infected B cells and from growth-arrested cells that had been drug-cured of parasites. Proliferation arrest led to a striking increase of PAG/Cbp expression; correspondingly, the amount of Csk associated with PAG/Cbp in GEMs increased markedly whereas PTK Hck accumulation in GEM fractions did not alter upon growth arrest. We propose that Theileria-induced lymphocyte proliferation and permanent activation of Hck stems from down-regulation of PAG/Cbp and the concomitant constitutive loss of the negative regulator Csk from the GEMs of transformed B cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Tauzin, H. Ding, K. Khatib, I. Ahmad, D. Burdevet, G. van Echten-Deckert, J. A. Lindquist, B. Schraven, N.-u. Din, B. Borisch, et al. Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine kinase in human B-NHL rafts Blood, February 15, 2008; 111(4): 2310 - 2320. [Abstract] [Full Text] [PDF] R. Lizundia, M. Chaussepied, M. Huerre, D. Werling, J. P. Di Santo, and G. Langsley c-Jun NH2-Terminal Kinase/c-Jun Signaling Promotes Survival and Metastasis of B Lymphocytes Transformed by Theileria. Cancer Res., June 15, 2006; 66(12): 6105 - 6110. [Abstract] [Full Text] [PDF] F. Zhu, B. Y. Choi, W.-Y. Ma, Z. Zhao, Y. Zhang, Y. Y. Cho, H. S. Choi, A. Imamoto, A. M. Bode, and Z. Dong COOH-Terminal Src Kinase-Mediated c-Jun Phosphorylation Promotes c-Jun Degradation and Inhibits Cell Transformation Cancer Res., June 1, 2006; 66(11): 5729 - 5736. [Abstract] [Full Text] [PDF] S. Munter, M. Way, and F. Frischknecht Signaling During Pathogen Infection Sci. Signal., May 16, 2006; 2006(335): re5 - re5. [Abstract] [Full Text] [PDF] S. Tedoldi, J. C. Paterson, M.-L. Hansmann, Y. Natkunam, T. Rudiger, P. Angelisova, M. Q. Du, H. Roberton, G. Roncador, L. Sanchez, et al. Transmembrane adaptor molecules: a new category of lymphoid-cell markers Blood, January 1, 2006; 107(1): 213 - 221. [Abstract] [Full Text] [PDF] N. Brdickova, T. Brdicka, P. Angelisova, O. Horvath, J. Spicka, I. Hilgert, J. Paces, L. Simeoni, S. Kliche, C. Merten, et al. LIME: A New Membrane Raft-associated Adaptor Protein Involved in CD4 and CD8 Coreceptor Signaling J. Exp. Med., November 17, 2003; 198(10): 1453 - 1462. [Abstract] [Full Text] [PDF]

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