|
|
Blood, 15 January 2005, Vol. 105, No. 2, pp. 552-561.
Prepublished online as a Blood First Edition Paper on June 22, 2004; DOI 10.1182/blood-2003-09-3237.
 Previous Article | Table of Contents | Next Article 
HEMATOPOIESIS
A novel role for STAT1 in regulating murine erythropoiesis: deletion of STAT1 results in overall reduction of erythroid progenitors and alters their distribution
Adrienne Halupa,
Monica L. Bailey,
Kai Huang,
Norman N. Iscove,
David E. Levy, and
Dwayne L. Barber
From the Departments of Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Division of Cellular and Molecular Biology, Ontario Cancer Institute, Department of Laboratory Medicine and Pathobiology, University Health Network, Toronto, ON, Canada; and Department of Pathology, New York University, New York, NY.
Erythropoietin (EPO) activates many distinct signal transduction cascades on engagement of its receptor. Deletion of the EPO, EPO receptor (EPO-R), or JAK2 genes in mice results in embryonic lethality due to a fatal anemia. EPO activates signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5a/b transcription factors in erythroid cell lines. Studies have focused on STAT5 as the primary target of EPO-dependent JAK2 activation. However, STAT5a/b–/– mice are viable, displaying a nonfatal anemia during embryogenesis, and delayed differentiation in adult erythropoiesis. Importantly, EPO-R cytoplasmic tyrosines are dispensable for viability in vivo. Interestingly, no cytoplasmic tyrosines are required for phosphorylation of STAT1. This led us to examine whether STAT1-deficient mice have altered erythropoiesis. A shift in erythropoiesis was observed in STAT1–/– mice, with reduced bone marrow-derived erythroid colony-forming units (CFU-Es) and a compensatory increase in splenic burst-forming units (BFU-Es) and CFU-Es. Both types of splenic-derived cells displayed EPO hyperresponsiveness. A 1.6-fold reduction in total CFU-Es was observed in STAT1-deficient mice, whereas total BFU-Es were comparable. Flow cytometry of STAT1-deficient erythroid cells revealed a less differentiated phenotype, associated with increased apoptosis of early erythroblasts. STAT1-deficient erythroblasts from phenylhydrazine-primed mice displayed enhanced phosphorylation of STAT5a/b, Erk1/2, and protein kinase B (PKB)/Akt. These results illustrate that STAT1 plays an important role in the regulation of erythropoiesis.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Ni, C. Zhao, G.-S. Feng, R. F. Paulson, and P. H. Correll
A Novel Stat3 Binding Motif in Gab2 Mediates Transformation of Primary Hematopoietic Cells by the Stk/Ron Receptor Tyrosine Kinase in Response to Friend Virus Infection
Mol. Cell. Biol.,
May 15, 2007;
27(10):
3708 - 3715.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. K. Mullarky, F. M. Szaba, L. W. Kummer, L. B. Wilhelm, M. A. Parent, L. L. Johnson, and S. T. Smiley
Gamma Interferon Suppresses Erythropoiesis via Interleukin-15
Infect. Immun.,
May 1, 2007;
75(5):
2630 - 2633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Dumitriu, M. R. Patrick, J. P. Petschek, S. Cherukuri, U. Klingmuller, P. L. Fox, and V. Lefebvre
Sox6 cell-autonomously stimulates erythroid cell survival, proliferation, and terminal maturation and is thereby an important enhancer of definitive erythropoiesis during mouse development
Blood,
August 15, 2006;
108(4):
1198 - 1207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Liu, R. Pop, C. Sadegh, C. Brugnara, V. H. Haase, and M. Socolovsky
Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo
Blood,
July 1, 2006;
108(1):
123 - 133.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Nishigaki, C. Hanson, T. Ohashi, A. Spadaccini, and S. Ruscetti
Erythroblast Transformation by the Friend Spleen Focus-Forming Virus Is Associated with a Block in Erythropoietin-Induced STAT1 Phosphorylation and DNA Binding and Correlates with High Expression of the Hematopoietic Phosphatase SHP-1.
J. Virol.,
June 1, 2006;
80(12):
5678 - 5685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Menon, J. Fang, and D. M. Wojchowski
Core erythropoietin receptor signals for late erythroblast development
Blood,
April 1, 2006;
107(7):
2662 - 2672.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G. Muntean and J. D. Crispino
Differential requirements for the activation domain and FOG-interaction surface of GATA-1 in megakaryocyte gene expression and development
Blood,
August 15, 2005;
106(4):
1223 - 1231.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
