|
|
 Previous Article | Table of Contents | Next Article 
Erythropoietin and interleukin-3 induce distinct events in erythropoietin
receptor-expressing BA/F3 cells
J Krosl, JE Damen, G Krystal and RK Humphries
Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, Canada.
To compare the signal transduction pathways used by erythropoietin (Ep) and
interleukin-3 (IL-3), the cDNA for the murine erythropoietin receptor (EpR)
was introduced into the IL-3-responsive cell lines Ba/F3 and DA-3 using
retrovirally mediated gene transfer. After selection in G418 and IL-3,
clones expressing comparable levels of cell surface EpR were identified
using biotinylated Ep and flow cytometry. A comparison of the effects of Ep
and IL-3 on these cells showed that most EpR+ Ba/F3 clones, when first
exposed to Ep, dramatically increased their levels of beta-globin mRNA. The
kinetics of appearance of this message after exposure to Ep varied
considerably from clone to clone, with some clones showing a marked
increase in beta-globin mRNA within 1 hour, while others required several
days before an increase was observed. Interestingly, not only was this
increase not seen with IL-3, but IL-3 prevented the Ep-induced appearance
of beta-globin message. On the other hand, none of the EpR+ DA-3 cell
clones tested increased their levels of beta-globin mRNA in response to Ep.
While the EpR+ DA-3 clones showed identical proliferative responses to IL-3
and Ep, most EpR+ Ba/F3 clones displayed a marked, albeit transient,
proliferative lag when first exposed to Ep. This was manifested as both an
increased doubling time in liquid culture and a decreased colony size in
methylcellulose. Plating efficiencies of EpR+ Ba/F3 cells in
methylcellulose, however, were identical in response to IL-3 and Ep,
suggesting that the Ep-induced lag in proliferation reflected a growth
delay of the entire population of cells to Ep rather than a selection of an
Ep-responsive subpopulation. Flow cytometric analysis established that this
growth delay was due to a lengthening of the first G1 period after exposure
to Ep. Interestingly, this Ep-induced delay in entry into the S phase was
not detected in cells stimulated with both Ep and IL-3 nor in EpR+ Ba/F3
cell clones that did not show an increase in beta-globin mRNA in response
to Ep. Thymidine-induced growth arrest, however, showed that delaying entry
into S phase alone was not sufficient to stimulate beta-globin mRNA in the
absence of Ep. Further studies established that the Ep-induced increase in
beta-globin mRNA could be inhibited by the tyrosine kinase inhibitor
genistein and the protein kinase C inhibitor Compound 3.(ABSTRACT TRUNCATED
AT 250 WORDS)
Volume 85,
Issue 1,
pp. 50-56,
01/01/1995
Copyright © 1995 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. Beslu, J. Krosl, M. Laurin, N. Mayotte, K. R. Humphries, and G. Sauvageau
Molecular interactions involved in HOXB4-induced activation of HSC self-renewal
Blood,
October 15, 2004;
104(8):
2307 - 2314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Damen, M. D. Ware, J. Kalesnikoff, M. R. Hughes, and G. Krystal
SHIP's C-terminus is essential for its hydrolysis of PIP3 and inhibition of mast cell degranulation
Blood,
March 1, 2001;
97(5):
1343 - 1351.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. C. Gregory, N. Jiang, K. Todokoro, J. Crouse, R. E. Pacifici, and D. M. Wojchowski
Erythropoietin Receptor and STAT5-Specific Pathways Promote SKT6 Cell Hemoglobinization
Blood,
August 15, 1998;
92(4):
1104 - 1118.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. W. Harris, X.-J. Hu, S. Schultz, M. O. Arcasoy, B. G. Forget, and N. Clare
The Distal Cytoplasmic Domain of the Erythropoietin Receptor Induces Granulocytic Differentiation in 32D Cells
Blood,
August 15, 1998;
92(4):
1219 - 1224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kirito, M. Uchida, M. Takatoku, K. Nakajima, T. Hirano, Y. Miura, and N. Komatsu
A Novel Function of Stat1alpha and Stat3 Proteins in Erythropoietin-Induced Erythroid Differentiation of a Human Leukemia Cell Line
Blood,
July 15, 1998;
92(2):
462 - 471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. E. Kowalski and D. L. Mager
A Human Endogenous Retrovirus Suppresses Translation of an Associated Fusion Transcript, PLA2L
J. Virol.,
July 1, 1998;
72(7):
6164 - 6168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ishiguro and A. C. Sartorelli
Clonal Variability in beta -Globin mRNA Content in an Interleukin-3-Dependent Bone Marrow Cell Line Transfected With the Erythropoietin Receptor Before and After Stimulation With Erythropoietin
Blood,
September 15, 1997;
90(6):
2273 - 2281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. T. Jubinsky, O. I. Krijanovski, D. G. Nathan, J. Tavernier, and C. A. Sieff
The beta Chain of the Interleukin-3 Receptor Functionally Associates With the Erythropoietin Receptor
Blood,
September 1, 1997;
90(5):
1867 - 1873.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Komatsu, K. Kirito, R. Shimizu, M. Kunitama, M. Yamada, M. Uchida, M. Takatoku, M. Eguchi, and Y. Miura
In Vitro Development of Erythroid and Megakaryocytic Cells From a UT-7 Subline, UT-7/GM
Blood,
June 1, 1997;
89(11):
4021 - 4033.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pless, K. Norga, M. Carroll, M. H. Heim, A. D. D'Andrea, and B. Mathey-Prevot
Receptors That Induce Erythroid Differentiation of Ba/F3 Cells: Structural Requirements and Effect on STAT5 Binding
Blood,
May 1, 1997;
89(9):
3175 - 3185.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Iwatsuki, T. Endo, H. Misawa, M. Yokouchi, A. Matsumoto, M. Ohtsubo, K. J. Mori, and A. Yoshimura
STAT5 Activation Correlates with Erythropoietin Receptor-mediated Erythroid Differentiation of an Erythroleukemia Cell Line
J. Biol. Chem.,
March 28, 1997;
272(13):
8149 - 8152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Feger, A. Dubart, C. Lacout, I. Dusanter-Fourt, P. Mayeux, W. Vainchenker, and D. Dumenil
Ectopic Expression of the Erythropoietin Receptor in a Murine Interleukin-6-Dependent Plasmacytoma Cell Line (TEPC-2027) Confers Proliferative Responsiveness to Erythropoietin
Blood,
January 15, 1997;
89(2):
435 - 445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Krosl, J. E. Damen, G. Krystal, and R.K. Humphries
Interleukin-3 (IL-3) Inhibits Erythropoietin-induced Differentiation in Ba/F3 Cells via the IL-3 Receptor alpha Subunit
J. Biol. Chem.,
November 1, 1996;
271(44):
27432 - 27437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T Hara and A Miyajima
Function and signal transduction mediated by the interleukin 3 receptor system in hematopoiesis
Stem Cells,
November 1, 1996;
14(6):
605 - 618.
[Abstract]
|
|
|
|
|
|
|
L. Liu, R. L. Cutler, and G. Krystal
Identification and Characterization of an Interleukin-3 Receptor-associated 110-kDa Serine/Threonine Kinase
J. Biol. Chem.,
September 22, 1995;
270(38):
22422 - 22427.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
