|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 94 No. 5 (September 1), 1999:
pp. 1601-1613
Megakaryocyte Growth and Development Factor-Induced Proliferation
and Differentiation Are Regulated by the Mitogen-Activated Protein
Kinase Pathway in Primitive Cord Blood Hematopoietic Progenitors
Serge Fichelson,
Jean-Marc Freyssinier,
Françoise Picard,
Michaela Fontenay-Roupie,
Martine Guesnu,
Mustapha Cherai,
Sylvie Gisselbrecht, and
Françoise Porteu
From the Laboratoire d'Hématopoièse, Site
Transfusionnel, the Laboratoire d'Hématologie, and the Institut
Cochin de Génétique Moléculaire (ICGM), Insitut
National de la Santé et de la Recherche Médicale (INSERM
U363), Hôpital Cochin, Université René Descartes,
Paris, France.
In several erythroleukemia cell lines, activation of
mitogen-activated protein kinases (MAPK) by phorbol esters or
megakaryocyte growth and development factor (MGDF) is required for
induction of megakaryocytic phenotype and growth arrest. To support
this model, we have examined the effect of a specific inhibitor of this
pathway (PD98059) on human CD34+ hematopoietic
progenitors isolated from cord blood (CB), induced to differentiate
along the megakaryocytic lineage in liquid cultures supplemented with
rhuMGDF. RhuMGDF induced a sustained activation of MAPK in
megakaryocytes and this activation was completely inhibited in the
presence of low concentrations of PD98059 (6 to 10 µmol/L). At this
concentration, PD98059 induced an increase in cell proliferation, resulting in accumulation of viable cells and a prolongation of the
life time of the cultures. This increase correlated with an increase in
DNA synthesis rather than with a reduction in apoptosis. This effect
was combined with developmental changes indicative of delayed
megakaryocytic differentiation: (1) PD98059-treated cells tended to
retain markers of immature progenitors as shown by the increased
proportion of both CD34+ and
CD41+CD34+ cells. (2) PD98059-treated
cultures were greatly enriched in immature blasts cells. (3) PD98059
increased megakaryocytic progenitors able to form colonies in semisolid
assays. Thus, the MAPK pathway, although not required for megakaryocyte
formation, seems to be involved in the transition from proliferation to
maturation in megakaryocytes. Inhibition of MAPK activation also led to
an increase in the number and size of erythroid colonies without
affecting granulocyte/macrophage progenitor numbers suggesting that, in addition to the megakaryocytic lineage, the MAPK pathway could play a
role in erythroid lineage differentiation.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
V. Hamelin, C. Letourneux, P.-H. Romeo, F. Porteu, and M. Gaudry
Thrombopoietin regulates IEX-1 gene expression through ERK-induced AML1 phosphorylation
Blood,
April 15, 2006;
107(8):
3106 - 3113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Guerriero, I. Parolini, U. Testa, P. Samoggia, E. Petrucci, M. Sargiacomo, C. Chelucci, M. Gabbianelli, and C. Peschle
Inhibition of TPO-induced MEK or mTOR activity induces opposite effects on the ploidy of human differentiating megakaryocytes
J. Cell Sci.,
February 15, 2006;
119(4):
744 - 752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. S. Stork and T. J. Dillon
Multiple roles of Rap1 in hematopoietic cells: complementary versus antagonistic functions
Blood,
November 1, 2005;
106(9):
2952 - 2961.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-C. Rouyez, M. Lestingi, M. Charon, S. Fichelson, A. Buzyn, and I. Dusanter-Fourt
IFN Regulatory Factor-2 Cooperates with STAT1 to Regulate Transporter Associated with Antigen Processing-1 Promoter Activity
J. Immunol.,
April 1, 2005;
174(7):
3948 - 3958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Nonami, R. Kato, K. Taniguchi, D. Yoshiga, T. Taketomi, S. Fukuyama, M. Harada, A. Sasaki, and A. Yoshimura
Spred-1 Negatively Regulates Interleukin-3-mediated ERK/Mitogen-activated Protein (MAP) Kinase Activation in Hematopoietic Cells
J. Biol. Chem.,
December 10, 2004;
279(50):
52543 - 52551.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Sabri, M. Jandrot-Perrus, J. Bertoglio, R. W. Farndale, V. M.-D. Mas, N. Debili, and W. Vainchenker
Differential regulation of actin stress fiber assembly and proplatelet formation by {alpha}2{beta}1 integrin and GPVI in human megakaryocytes
Blood,
November 15, 2004;
104(10):
3117 - 3125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Rudin, J. L. Marshall, C. H. Huang, H. L. Kindler, C. Zhang, D. Kumar, P. C. Gokhale, J. Steinberg, S. Wanaski, U. N. Kasid, et al.
Delivery of a Liposomal c-raf-1 Antisense Oligonucleotide by Weekly Bolus Dosing in Patients with Advanced Solid Tumors: A Phase I Study
Clin. Cancer Res.,
November 1, 2004;
10(21):
7244 - 7251.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-M. Paulus, N. Debili, F. Larbret, J. Levin, and W. Vainchenker
Thrombopoietin responsiveness reflects the number of doublings undergone by megakaryocyte progenitors
Blood,
October 15, 2004;
104(8):
2291 - 2298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kamata, C. A. Pritchard, and A. D. Leavitt
Raf-1 is not required for megakaryocytopoiesis or TPO-induced ERK phosphorylation
Blood,
April 1, 2004;
103(7):
2568 - 2570.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Nobuhisa, R. Kato, H. Inoue, M. Takizawa, K. Okita, A. Yoshimura, and T. Taga
Spred-2 Suppresses Aorta-Gonad-Mesonephros Hematopoiesis by Inhibiting MAP Kinase Activation
J. Exp. Med.,
March 1, 2004;
199(5):
737 - 742.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. L. Delehanty, M. Mogass, S. L. Gonias, F. K. Racke, B. Johnstone, and A. N. Goldfarb
Stromal inhibition of megakaryocytic differentiation is associated with blockade of sustained Rap1 activation
Blood,
March 1, 2003;
101(5):
1744 - 1751.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Casella, T. Feccia, C. Chelucci, P. Samoggia, G. Castelli, R. Guerriero, I. Parolini, E. Petrucci, E. Pelosi, O. Morsilli, et al.
Autocrine-paracrine VEGF loops potentiate the maturation of megakaryocytic precursors through Flt1 receptor
Blood,
February 15, 2003;
101(4):
1316 - 1323.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-K. Boer, A. L. Drayer, H. Rui, and E. Vellenga
Prostaglandin-E2 enhances EPO-mediated STAT5 transcriptional activity by serine phosphorylation of CREB
Blood,
June 28, 2002;
100(2):
467 - 473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Meunier, D. Bordereaux, F. Porteu, S. Gisselbrecht, S. Chretien, and G. Courtois
Cloning and Characterization of a Family of Proteins Associated with Mpl
J. Biol. Chem.,
March 8, 2002;
277(11):
9139 - 9147.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-J. Lataillade, D. Clay, P. Bourin, F. Herodin, C. Dupuy, C. Jasmin, and M.-C. Le Bousse-Kerdiles
Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G0/G1 transition in CD34+ cells: evidence for an autocrine/paracrine mechanism
Blood,
February 15, 2002;
99(4):
1117 - 1129.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-D. Filippi, F. Porteu, F. L. Pesteur, V. Schiavon, G. A. Millot, W. Vainchenker, F. J. de Sauvage, A. Dubart Kupperschmitt, and F. Sainteny
Requirement for mitogen-activated protein kinase activation in the response of embryonic stem cell-derived hematopoietic cells to thrombopoietin in vitro
Blood,
February 15, 2002;
99(4):
1174 - 1182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. F. Dorsey, J. M. Cunnick, S. M. Mane, and J. Wu
Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation of Bcr-Abl+ K562 leukemic cells by Gab2
Blood,
February 15, 2002;
99(4):
1388 - 1397.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. A. Millot, W. Vainchenker, D. Dumenil, and F. Svinarchuk
Distinct effects of thrombopoietin depending on a threshold level of activated Mpl in BaF-3 cells
J. Cell Sci.,
January 6, 2002;
115(11):
2329 - 2337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Wu, H.-W. Shen, T.-F. Wu, L. F. Brass, and K.-C. Sung
Extracellular Signal-Regulated Kinases and G Protein-Coupled Receptors in Megakaryocytic Human Erythroleukemia Cells: Selective Activation, Differential Regulation, and Dissociation from Mitogenesis
J. Pharmacol. Exp. Ther.,
January 1, 2002;
300(1):
339 - 345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Guerriero, G. Mattia, U. Testa, C. Chelucci, G. Macioce, I. Casella, P. Samoggia, C. Peschle, and H. J. Hassan
Stromal cell-derived factor 1{alpha} increases polyploidization of megakaryocytes generated by human hematopoietic progenitor cells
Blood,
May 1, 2001;
97(9):
2587 - 2595.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Garcia, J. de Gunzburg, A. Eychène, S. Gisselbrecht, and F. Porteu
Thrombopoietin-Mediated Sustained Activation of Extracellular Signal-Regulated Kinase in UT7-Mpl Cells Requires Both Ras-Raf-1- and Rap1-B-Raf-Dependent Pathways
Mol. Cell. Biol.,
April 15, 2001;
21(8):
2659 - 2670.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Gaur, G. J. Murphy, F. J. deSauvage, and A. D. Leavitt
Characterization of Mpl mutants using primary megakaryocyte-lineage cells from mpl{-}/{-} mice: a new system for Mpl structure-function studies
Blood,
March 15, 2001;
97(6):
1653 - 1661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kawasaki, I. Matsumura, J.-i. Miyagawa, S. Ezoe, H. Tanaka, Y. Terada, M. Tatsuka, T. Machii, H. Miyazaki, Y. Furukawa, et al.
Downregulation of an AIM-1 Kinase Couples with Megakaryocytic Polyploidization of Human Hematopoietic Cells
J. Cell Biol.,
January 16, 2001;
152(2):
275 - 288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Majka, A. Janowska-Wieczorek, J. Ratajczak, M. A. Kowalska, G. Vilaire, Z. K. Pan, M. Honczarenko, L. A. Marquez, M. Poncz, and M. Z. Ratajczak
Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis
Blood,
December 15, 2000;
96(13):
4142 - 4151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Matsumura, A. Kawasaki, H. Tanaka, J. Sonoyama, S. Ezoe, N. Minegishi, K. Nakajima, M. Yamamoto, and Y. Kanakura
Biologic significance of GATA-1 activities in Ras-mediated megakaryocytic differentiation of hematopoietic cell lines
Blood,
October 1, 2000;
96(7):
2440 - 2450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. K. Racke, D. Wang, Z. Zaidi, J. Kelley, J. Visvader, J.-W. Soh, and A. N. Goldfarb
A Potential Role for Protein Kinase C-epsilon in Regulating Megakaryocytic Lineage Commitment
J. Biol. Chem.,
January 5, 2001;
276(1):
522 - 528.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. Goldfarb, L. L. Delehanty, D. Wang, F. K. Racke, and I. M. Hussaini
Stromal Inhibition of Megakaryocytic Differentiation Correlates with Blockade of Signaling by Protein Kinase C-epsilon and ERK/MAPK
J. Biol. Chem.,
July 27, 2001;
276(31):
29526 - 29530.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
