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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0089. This Article Full Text (PDF) All Versions of this Article: 2002-01-0089v1 100/3/954    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 Schulze-Luehrmann, J. Articles by Serfling, E. Search for Related Content PubMed PubMed Citation Articles by Schulze-Luehrmann, J. Articles by Serfling, E. Social Bookmarking                   What's this? Submitted January 14, 2002 Accepted April 2, 2002 Hematopoietic Progenitor Kinase 1 (HPK1) supports Apoptosis of T Lymphocytes Jan Schulze-Luehrmann, Brigitte Santner-Nanan, Mithilesh K Jha, Anneliese Schimpl, Andris Avots, and Edgar Serfling* Molecular Pathology, Institute of Pathology, Wuerzburg, Germany Institute of Virology and Immunobiology, Wuerzburg, Germany Molecular Pathology, Institute of Pathology, Wuerzburg, Germany; Molecular Epigenetics Group, Institute of Medical Radiation and Cell Research (MSZ), Wuerzburg, Germany * Corresponding author; email: path015{at}mail.uni-wuerzburg.de. Hematopoietic progenitor kinase 1 (HPK1) is a member of germinal center kinases that is predominantly expressed in hematopoietic cells and transiently activated by T cell receptor (TCR) triggering. We show here that HPK1 supports apoptosis of T cells. When HPK1 was overexpressed in murine CD4+ T cells a substantial increase was observed in spontaneous and TCR/CD3-mediated apoptosis as well as in Fas ligand (FasL) expression. In H202-treated EL-4 thymoma cells, which show an increase in reactive oxygen species (ROS) and apoptosis, overexpression of HPK1 enhanced ROS-mediated apoptosis whereas expression of HPK1 anti-sense (AS) RNA impaired apoptosis. HPK1 expression also led to a sustained increase in c-Jun N-terminal kinase (JNK) activity suggesting that JNK activation contributes to the HPK1-mediated apoptosis in H202-treated EL-4 cells. Under the same conditions a rapid cleavage of HPK1 was observed, and overexpression of N- and C-terminal cleavage products in CD4+ T cells resulted, similar to full-length HPK1, in an increase in apoptosis. In agreement with published data we show that the C-terminal portion of HPK1 suppresses IB degradation thereby inhibiting NF-B activation.These findings suggest that by inhibiting the anti-apoptotic action of NF-B and inducing the pro-apoptotic activity of JNK, HPK1 supports apoptosis in T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Brenner, M. Brechmann, S. Rohling, M. Tapernoux, T. Mock, D. Winter, W. D. Lehmann, F. Kiefer, M. Thome, P. H. Krammer, et al. Phosphorylation of CARMA1 by HPK1 is critical for NF-{kappa}B activation in T cells PNAS, August 25, 2009; 106(34): 14508 - 14513. [Abstract] [Full Text] [PDF] S. Alzabin, N. Bhardwaj, F. Kiefer, S. Sawasdikosol, and S. Burakoff Hematopoietic Progenitor Kinase 1 Is a Negative Regulator of Dendritic Cell Activation J. Immunol., May 15, 2009; 182(10): 6187 - 6194. [Abstract] [Full Text] [PDF] D. Brenner, A. Golks, M. Becker, W. Muller, C. R. Frey, R. Novak, D. Melamed, F. Kiefer, P. H. Krammer, and R. Arnold Caspase-cleaved HPK1 induces CD95L-independent activation-induced cell death in T and B lymphocytes Blood, December 1, 2007; 110(12): 3968 - 3977. [Abstract] [Full Text] [PDF] S. Sawasdikosol, S. Pyarajan, S. Alzabin, G. Matejovic, and S. J. Burakoff Prostaglandin E2 Activates HPK1 Kinase Activity via a PKA-dependent Pathway J. Biol. Chem., November 30, 2007; 282(48): 34693 - 34699. [Abstract] [Full Text] [PDF] M. Y. Yang, S. S. Lau, and T. J. Monks 2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ)-Mediated Apoptosis of Human Promyelocytic Leukemia Cells Is Preceded by Mitochondrial Cytochrome c Release in the Absence of a Decrease in the Mitochondrial Membrane Potential Toxicol. Sci., July 1, 2005; 86(1): 92 - 100. [Abstract] [Full Text] [PDF] R. Arnold, I. M. Patzak, B. Neuhaus, S. Vancauwenbergh, A. Veillette, J. Van Lint, and F. Kiefer Activation of Hematopoietic Progenitor Kinase 1 Involves Relocation, Autophosphorylation, and Transphosphorylation by Protein Kinase D1 Mol. Cell. Biol., March 15, 2005; 25(6): 2364 - 2383. [Abstract] [Full Text] [PDF] G. Zhou, J. S. Boomer, and T.-H. Tan Protein Phosphatase 4 Is a Positive Regulator of Hematopoietic Progenitor Kinase 1 J. Biol. Chem., November 19, 2004; 279(47): 49551 - 49561. [Abstract] [Full Text] [PDF]

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