|
|
Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3347-3354
Activation of Hematopoietic Progenitor Kinase-1 by Erythropoietin
Yuka Nagata,
Friedemann Kiefer,
Takeshi Watanabe, and
Kazuo Todokoro
From the Tsukuba Life Science Center, The Institute of Physical and
Chemical Research (RIKEN), Ibaraki, Japan; the Max-Planck-Institute for
Physiological and Clinical Research, W.G. Kerckhoff-Institute, Bad
Nauheim, Germany; and the Medical Institute of Bioregulation, Kyushu
University, Fukuoka, Japan.
Hematopoietic progenitor kinase-1 (HPK1), which is expressed
predominantly in hematopoietic cells, was identified as a mammalian Ste20 homologue that, upon transfection, leads to activation of JNK/SAPK in nonhematopoietic cells. The JNK/SAPK pathway is activated by various environmental stresses and proinflammatory and hematopoietic cytokines. Upstream activators of HPK1 currently remain elusive, and
its precise role in hematopoiesis has yet to be defined. We therefore
examined the possible involvement of HPK1 in erythropoietin (Epo) and
environmental stress-induced JNK/SAPK activation in the Epo-dependent
FD-EPO cells and Epo-responsive SKT6 cells. We found that Epo, but not
environmental stresses, induced rapid and transient activation of HPK1,
whereas both induced activation of JNK/SAPK. A screen for HPK1 binding
proteins identified the hematopoietic cell-specific protein 1 (HS1) as
a potential HPK1 interaction partner. We found HPK1 constitutively
associated with HS1 and that HS1 was tyrosine-phosphorylated in
response to cellular stresses as well as Epo stimulation. Furthermore,
antisense oligonucleotides to HPK1 suppressed Epo-dependent cell growth
and Epo-induced erythroid differentiation. We therefore conclude that
Epo induces activation of both HPK1 and HS1, whereas cellular stresses
activate only HS1, and that the HPK1-JNK/SAPK pathway is involved in
Epo-induced growth and differentiation signals.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
H. Wang, X. Song, C. Logsdon, G. Zhou, D. B. Evans, J. L. Abbruzzese, S. R. Hamilton, T.-H. Tan, and H. Wang
Proteasome-Mediated Degradation and Functions of Hematopoietic Progenitor Kinase 1 in Pancreatic Cancer
Cancer Res.,
February 1, 2009;
69(3):
1063 - 1070.
[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]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
S. K. Liu, C. A. Smith, R. Arnold, F. Kiefer, and C. J. McGlade
The Adaptor Protein Gads (Grb2-Related Adaptor Downstream of Shc) Is Implicated in Coupling Hemopoietic Progenitor Kinase-1 to the Activated TCR
J. Immunol.,
August 1, 2000;
165(3):
1417 - 1426.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Ingley, M. K. Sarna, J. G. Beaumont, P. A. Tilbrook, S. Tsai, Y. Takemoto, J. H. Williams, and S. P. Klinken
HS1 Interacts with Lyn and Is Critical for Erythropoietin-induced Differentiation of Erythroid Cells
J. Biol. Chem.,
March 10, 2000;
275(11):
7887 - 7893.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Arnold, J. Liou, H. C. A. Drexler, A. Weiss, and F. Kiefer
Caspase-mediated Cleavage of Hematopoietic Progenitor Kinase 1 (HPK1) Converts an Activator of NFkappa B into an Inhibitor of NFkappa B
J. Biol. Chem.,
April 27, 2001;
276(18):
14675 - 14684.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|