| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 18, 14675-14684, May 4, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Hematopoietic progenitor kinase 1 (HPK1), a
mammalian Ste20-related protein kinase, is a potent stimulator of the
stress-activated protein kinases (SAPKs/JNKs). Here we report
activation of NF
Caspase-mediated Cleavage of Hematopoietic Progenitor Kinase 1 (HPK1) Converts an Activator of NF
B into an Inhibitor of NFB*
,,¶
Max-Planck Institute for Physiological and
Clinical Research, W. G. Kerckhoff Institute, Parkstrasse 1, D-61231 Bad Nauheim, Germany and § Departments of
Medicine and Microbiology and Immunology, Howard Hughes Medical
Institute, University of California,
San Francisco, California 94143-0795
B transcription factors by HPK1 that was independent
of SAPK/JNK activation. Overexpression of a dominant-negative SEK1
significantly inhibited SAPK/JNK activation, whereas NFB stimulation
by HPK1 remained unaffected. Furthermore, activation of NFB required the presence of full-length, kinase-active HPK1, whereas the isolated kinase domain of HPK1 was sufficient for activation of SAPK/JNK. We
also demonstrate that overexpression of a dominant-negative IKK
blocks HPK1-mediated NFB activation suggesting that HPK1 acts
upstream of the IB kinase complex. In apoptotic myeloid progenitor cells HPK1 was cleaved at a DDVD motif resulting in the
release of the kinase domain and a C-terminal part. Although expression
of the isolated HPK1 kinase domain led to SAPK/JNK activation, the
C-terminal part inhibited NFB activation. This dominant-negative
effect was not only restricted to HPK1-mediated but also to NIK- and
tumor necrosis factor 
-mediated NFB activation, suggesting an
impairment of the IB kinase complex. Thus HPK1 activates both the
SAPK/JNK and NFB pathway in hematopoietic cells but is converted
into an inhibitor of NFB activation in apoptotic cells.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
M. Lewitzky, M. Harkiolaki, M.-C. Domart, E. Y. Jones, and S. M. Feller Mona/Gads SH3C Binding to Hematopoietic Progenitor Kinase 1 (HPK1) Combines an Atypical SH3 Binding Motif, R/KXXK, with a Classical PXXP Motif Embedded in a Polyproline Type II (PPII) Helix J. Biol. Chem., July 2, 2004; 279(27): 28724 - 28732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Jiang, S. A. Wek, B. C. McGrath, D. Scheuner, R. J. Kaufman, D. R. Cavener, and R. C. Wek Phosphorylation of the {alpha} Subunit of Eukaryotic Initiation Factor 2 Is Required for Activation of NF-{kappa}B in Response to Diverse Cellular Stresses Mol. Cell. Biol., August 15, 2003; 23(16): 5651 - 5663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Schulze-Luehrmann, B. Santner-Nanan, M. K. Jha, A. Schimpl, A. Avots, and E. Serfling Hematopoietic progenitor kinase 1 supports apoptosis of T lymphocytes Blood, July 18, 2002; 100(3): 954 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yu, C. Riou, D. Davidson, R. Minhas, J. D. Robson, M. Julius, R. Arnold, F. Kiefer, and A. Veillette Synergistic Regulation of Immunoreceptor Signaling by SLP-76-Related Adaptor Clnk and Serine/Threonine Protein Kinase HPK-1 Mol. Cell. Biol., September 15, 2001; 21(18): 6102 - 6112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tsuji, M. Okamoto, K. Yamada, N. Okamoto, R. Goitsuka, R. Arnold, F. Kiefer, and D. Kitamura B Cell Adaptor Containing Src Homology 2 Domain (BASH) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1 J. Exp. Med., August 20, 2001; 194(4): 529 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sauer, J. Liou, S. B. Singh, D. Yablonski, A. Weiss, and R. M. Perlmutter Hematopoietic Progenitor Kinase 1 Associates Physically and Functionally with the Adaptor Proteins B Cell Linker Protein and SLP-76 in Lymphocytes J. Biol. Chem., November 21, 2001; 276(48): 45207 - 45216. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
