|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3757-3773
Protein Kinase B (c-Akt), Phosphatidylinositol 3-Kinase, and STAT5
Are Activated by Erythropoietin (EPO) in HCD57 Erythroid Cells But
Are Constitutively Active in an EPO-Independent,
Apoptosis-Resistant Subclone (HCD57-SREI Cells)
Haifeng Bao,
Sarah M. Jacobs-Helber,
Amy E. Lawson,
Kalyani Penta,
Amittha Wickrema, and
Stephen T. Sawyer
From the Department of Pharmacology and Toxicology, Medical College
of Virginia campus of Virginia Commonwealth University, Richmond, VA;
the Department of Medicine, Stanford University, San Francisco, CA; and
Hematopoietic Stem Cell Laboratory, University of Illinois, Chicago,
IL.
We found that erythropoietin (EPO) and stem cell factor (SCF)
activated protein kinase B (PKB/Akt) in EPO-dependent HCD57 erythroid
cells. To better understand signals controlling proliferation and
viability, erythroid cells that resist apoptosis in the absence of EPO
were subcloned and characterized (HCD57-SREI cells). Constitutive activations of PKB/Akt, STAT5a, and STAT5b were noted in these EPO-independent cells. PI3-kinase activity was an upstream activator of
PKB/Akt because the PI3-kinase inhibitor LY294002 blocked
both constitutive PKB/Akt and factor-dependent PKB/Akt activity. The LY294002 study showed that proliferation and viability of both HCD57-SREI and HCD57 cells correlated with the activity of PKB/Akt; however, PKB/Akt activity alone did not protect these cells from apoptosis. Treatment of HCD57 cells with SCF also activated PKB/Akt, but did not protect from apoptosis. This result suggested that PKB/PI3-kinase activity is necessary but not sufficient to promote viability and/or proliferation. Constitutive STAT5 activity, activated through an unknown pathway not including JAK2 or EPOR, may act in
concert with the constitutive PI3-kinase/PKB/Akt pathway to protect the
EPO-independent HCD57-SREI cells from apoptosis and promote limited proliferation.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. K. Salahudeen, N. Haider, J. Jenkins, M. Joshi, H. Patel, H. Huang, M. Yang, and H. Zhe
Antiapoptotic properties of erythropoiesis-stimulating proteins in models of cisplatin-induced acute kidney injury
Am J Physiol Renal Physiol,
June 1, 2008;
294(6):
F1354 - F1365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Paffett-Lugassy, N. Hsia, P. G. Fraenkel, B. Paw, I. Leshinsky, B. Barut, N. Bahary, J. Caro, R. Handin, and L. I. Zon
Functional conservation of erythropoietin signaling in zebrafish
Blood,
October 1, 2007;
110(7):
2718 - 2726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Rimmele, O. Kosmider, P. Mayeux, F. Moreau-Gachelin, and C. Guillouf
Spi-1/PU.1 participates in erythroleukemogenesis by inhibiting apoptosis in cooperation with Epo signaling and by blocking erythroid differentiation
Blood,
April 1, 2007;
109(7):
3007 - 3014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Ingley, J. R. Schneider, C. J. Payne, D. J. McCarthy, K. W. Harder, M. L. Hibbs, and S. P. Klinken
Csk-binding Protein Mediates Sequential Enzymatic Down-regulation and Degradation of Lyn in Erythropoietin-stimulated Cells
J. Biol. Chem.,
October 20, 2006;
281(42):
31920 - 31929.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Gewirtz, X. Di, T. D. Walker, and S. T. Sawyer
Erythropoietin fails to interfere with the antiproliferative and cytotoxic effects of antitumor drugs.
Clin. Cancer Res.,
April 1, 2006;
12(7):
2232 - 2238.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Dallalio, E. Law, and R. T. Means Jr
Hepcidin inhibits in vitro erythroid colony formation at reduced erythropoietin concentrations
Blood,
April 1, 2006;
107(7):
2702 - 2704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Zhao, C. Kitidis, M. D. Fleming, H. F. Lodish, and S. Ghaffari
Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase/AKT signaling pathway
Blood,
February 1, 2006;
107(3):
907 - 915.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Munugalavadla, L. C. Dore, B. L. Tan, L. Hong, M. Vishnu, M. J. Weiss, and R. Kapur
Repression of c-Kit and Its Downstream Substrates by GATA-1 Inhibits Cell Proliferation during Erythroid Maturation
Mol. Cell. Biol.,
August 1, 2005;
25(15):
6747 - 6759.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sugatani and K. A. Hruska
Akt1/Akt2 and Mammalian Target of Rapamycin/Bim Play Critical Roles in Osteoclast Differentiation and Survival, Respectively, Whereas Akt Is Dispensable for Cell Survival in Isolated Osteoclast Precursors
J. Biol. Chem.,
February 4, 2005;
280(5):
3583 - 3589.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Wandzioch, C. E. Edling, R. H. Palmer, L. Carlsson, and B. Hallberg
Activation of the MAP kinase pathway by c-Kit is PI-3 kinase dependent in hematopoietic progenitor/stem cell lines
Blood,
July 1, 2004;
104(1):
51 - 57.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Bakker, M. Blazquez-Domingo, A. Kolbus, J. Besooyen, P. Steinlein, H. Beug, P. J. Coffer, B. Lowenberg, M. von Lindern, and T. B. van Dijk
FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1
J. Cell Biol.,
January 19, 2004;
164(2):
175 - 184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Myssina, S. M. Huber, C. Birka, P. A. Lang, K. S. Lang, B. Friedrich, T. Risler, T. Wieder, and F. Lang
Inhibition of Erythrocyte Cation Channels by Erythropoietin
J. Am. Soc. Nephrol.,
November 1, 2003;
14(11):
2750 - 2757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J Smith, A. J Bleyer, W. C Little, and D. C Sane
The cardiovascular effects of erythropoietin
Cardiovasc Res,
September 1, 2003;
59(3):
538 - 548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Huddleston, B. Tan, F.-C. Yang, H. White, M. J. Wenning, A. Orazi, M. C. Yoder, R. Kapur, and D. A. Ingram
Functional p85{alpha} gene is required for normal murine fetal erythropoiesis
Blood,
July 1, 2003;
102(1):
142 - 145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ruscher, D. Freyer, M. Karsch, N. Isaev, D. Megow, B. Sawitzki, J. Priller, U. Dirnagl, and A. Meisel
Erythropoietin Is a Paracrine Mediator of Ischemic Tolerance in the Brain: Evidence from an In Vitro Model
J. Neurosci.,
December 1, 2002;
22(23):
10291 - 10301.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Lin, L. Brown, D. W. Hedley, D. L. Barber, and S. Benchimol
The death-promoting activity of p53 can be inhibited by distinct signaling pathways
Blood,
December 1, 2002;
100(12):
3990 - 4000.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Haq, A. Halupa, B. K. Beattie, J. M. Mason, B. W. Zanke, and D. L. Barber
Regulation of Erythropoietin-induced STAT Serine Phosphorylation by Distinct Mitogen-activated Protein Kinases
J. Biol. Chem.,
May 3, 2002;
277(19):
17359 - 17366.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Guasch, V. Ollendorff, J.-P. Borg, D. Birnbaum, and M.-J. Pebusque
8p12 Stem Cell Myeloproliferative Disorder: the FOP-Fibroblast Growth Factor Receptor 1 Fusion Protein of the t(6;8) Translocation Induces Cell Survival Mediated by Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase/Akt/mTOR Pathways
Mol. Cell. Biol.,
December 1, 2001;
21(23):
8129 - 8142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ghaffari, C. Kitidis, M. D. Fleming, H. Neubauer, K. Pfeffer, and H. F. Lodish
Erythropoiesis in the absence of janus-kinase 2: BCR-ABL induces red cell formation in JAK2-/- hematopoietic progenitors
Blood,
November 15, 2001;
98(10):
2948 - 2957.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Barnache, P. Mayeux, B. Payrastre, and F. Moreau-Gachelin
Alterations of the phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways in the erythropoietin-independent Spi-1/PU.1 transgenic proerythroblasts
Blood,
October 15, 2001;
98(8):
2372 - 2381.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. C. P. Somervaille, D. C. Linch, and A. Khwaja
Growth factor withdrawal from primary human erythroid progenitors induces apoptosis through a pathway involving glycogen synthase kinase-3 and Bax
Blood,
September 1, 2001;
98(5):
1374 - 1381.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. K. Henry, J. T. Lynch, A. K. Eapen, and F. W. Quelle
DNA damage-induced cell-cycle arrest of hematopoietic cells is overridden by activation of the PI-3 kinase/Akt signaling pathway
Blood,
August 1, 2001;
98(3):
834 - 841.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Shinjyo, R. Kuribara, T. Inukai, H. Hosoi, T. Kinoshita, A. Miyajima, P. J. Houghton, A. T. Look, K. Ozawa, and T. Inaba
Downregulation of Bim, a Proapoptotic Relative of Bcl-2, Is a Pivotal Step in Cytokine-Initiated Survival Signaling in Murine Hematopoietic Progenitors
Mol. Cell. Biol.,
February 1, 2001;
21(3):
854 - 864.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. W. Muszynski, D. Thompson, C. Hanson, R. Lyons, A. Spadaccini, and S. K. Ruscetti
Growth Factor-Independent Proliferation of Erythroid Cells Infected with Friend Spleen Focus-Forming Virus Is Protein Kinase C Dependent but Does Not Require Ras-GTP
J. Virol.,
September 15, 2000;
74(18):
8444 - 8451.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. E. Lawson, H. Bao, A. Wickrema, S. M. Jacobs-Helber, and S. T. Sawyer
Phosphatase inhibition promotes antiapoptotic but not proliferative signaling pathways in erythropoietin-dependent HCD57 cells
Blood,
September 15, 2000;
96(6):
2084 - 2092.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Jacobs-Helber, J. J. Ryan, and S. T. Sawyer
JNK and p38 are activated by erythropoietin (EPO) but are not induced in apoptosis following EPO withdrawal in EPO-dependent HCD57 cells
Blood,
August 1, 2000;
96(3):
933 - 940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kashii, M. Uchida, K. Kirito, M. Tanaka, K. Nishijima, M. Toshima, T. Ando, K. Koizumi, T. Endoh, K.-i. Sawada, et al.
A member of Forkhead family transcription factor, FKHRL1, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction
Blood,
August 1, 2000;
96(3):
941 - 949.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Nishigaki, C. Hanson, T. Ohashi, D. Thompson, K. Muszynski, and S. Ruscetti
Erythroid Cells Rendered Erythropoietin Independent by Infection with Friend Spleen Focus-Forming Virus Show Constitutive Activation of Phosphatidylinositol 3-Kinase and Akt Kinase: Involvement of Insulin Receptor Substrate-Related Adapter Proteins
J. Virol.,
April 1, 2000;
74(7):
3037 - 3045.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Y. Miyakawa, P. Rojnuckarin, T. Habib, and K. Kaushansky
Thrombopoietin Induces Phosphoinositol 3-Kinase Activation through SHP2, Gab, and Insulin Receptor Substrate Proteins in BAF3 Cells and Primary Murine Megakaryocytes
J. Biol. Chem.,
January 19, 2001;
276(4):
2494 - 2502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kusch, S. Tkachuk, H. Haller, R. Dietz, D. C. Gulba, M. Lipp, and I. Dumler
Urokinase Stimulates Human Vascular Smooth Muscle Cell Migration via a Phosphatidylinositol 3-Kinase-Tyk2 Interaction
J. Biol. Chem.,
December 8, 2000;
275(50):
39466 - 39473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Tanaka, K. Kirito, Y. Kashii, M. Uchida, T. Watanabe, H. Endo, T. Endoh, K.-i. Sawada, K. Ozawa, and N. Komatsu
Forkhead Family Transcription Factor FKHRL1 Is Expressed in Human Megakaryocytes. REGULATION OF CELL CYCLING AS A DOWNSTREAM MOLECULE OF THROMBOPOIETIN SIGNALING
J. Biol. Chem.,
April 27, 2001;
276(18):
15082 - 15089.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
