|
|
 Previous Article | Table of Contents | Next Article 
Activation of the Mitogen-Activated Protein Kinase Pathway Is Involved in and Sufficient for Megakaryocytic Differentiation of CMK Cells
Allen S. Melemed,
John W. Ryder, and
Terry A. Vik
From the James Whitcomb Riley Hospital for Children and Herman B Wells Center for Pediatric Research, Section of Pediatric Hematology/Oncology; and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN.
Activation of the mitogen-activated protein (MAP) kinase pathway has been associated with both cell proliferation and differentiation. Constitutively activated forms of Mek (MAP kinase/Erk kinase) and Erk (MAP kinase) have been previously shown capable of inducing differentiation or proliferation in nonhematopoietic cells. To specifically examine the role of Erk activation in megakaryocytic growth and development, we activated the MAP kinase pathway by the transfection of constitutively activated Mek or Erk cDNA into a human megakaryoblastic cell line, CMK, by electroporation. The CMK transfectant clones that expressed constitutively activated Mek or Erk showed morphologic changes of differentiation. Transfected cells also showed expression of mature megakaryocytic cell surface markers. The MAP kinase pathway was also activated by treatment of the hematopoietic cells with a cytokine that activates Erk. The treatment of CMK cells with stem cell factor (SCF ) caused MAP kinase activation and induced differentiation by the expression of mature megakaryocytic cell surface markers. The effects of the SCF treatment were inhibited by pretreatment with a specific inhibitor of the MAP kinase pathway, PD98059. In this report, we conclude that activation of the MAP kinase pathway was both necessary and sufficient to induce differentiation in this megakaryoblastic cell line.
Blood, Vol. 90 No. 9 (November 1), 1997:
pp. 3462-3470
© 1997 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:
|
|
|
|
 
A. F. Valledor, L. Arpa, E. Sanchez-Tillo, M. Comalada, C. Casals, J. Xaus, C. Caelles, J. Lloberas, and A. Celada
IFN-{gamma}-mediated inhibition of MAPK phosphatase expression results in prolonged MAPK activity in response to M-CSF and inhibition of proliferation
Blood,
October 15, 2008;
112(8):
3274 - 3282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. Kang, D. H. Lee, H. Seo, J. S. Park, K. H. Nam, S. Y. Shin, C.-S. Park, and I. Y. Chung
Regulation of Functional Phenotypes of Cord Blood Derived Eosinophils by {gamma}-Secretase Inhibitor
Am. J. Respir. Cell Mol. Biol.,
November 1, 2007;
37(5):
571 - 577.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
N. Ajenjo, E. Canon, I. Sanchez-Perez, D. Matallanas, J. Leon, R. Perona, and P. Crespo
Subcellular Localization Determines the Protective Effects of Activated ERK2 against Distinct Apoptogenic Stimuli in Myeloid Leukemia Cells
J. Biol. Chem.,
July 30, 2004;
279(31):
32813 - 32823.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Sevinsky, A. M. Whalen, and N. G. Ahn
Extracellular Signal-Regulated Kinase Induces the Megakaryocyte GPIIb/CD41 Gene through MafB/Kreisler
Mol. Cell. Biol.,
May 15, 2004;
24(10):
4534 - 4545.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Lannutti and J. G. Drachman
Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of hematopoietic cell lines and primary megakaryocytic progenitors
Blood,
May 15, 2004;
103(10):
3736 - 3743.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
T. Adachi, B. K. Choudhury, S. Stafford, S. Sur, and R. Alam
The Differential Role of Extracellular Signal-Regulated Kinases and p38 Mitogen-Activated Protein Kinase in Eosinophil Functions
J. Immunol.,
August 15, 2000;
165(4):
2198 - 2204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Ajenjo, D. S. Aaronson, E. Ceballos, C. Richard, J. Leon, and P. Crespo
Myeloid Leukemia Cell Growth and Differentiation Are Independent of Mitogen-activated Protein Kinase ERK1/2 Activation
J. Biol. Chem.,
March 15, 2000;
275(10):
7189 - 7197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Matsumura, H. Tanaka, A. Kawasaki, J. Odajima, H. Daino, K. Hashimoto, H. Wakao, K. Nakajima, T. Kato, H. Miyazaki, et al.
Increased D-type Cyclin Expression Together with Decreased cdc2 Activity Confers Megakaryocytic Differentiation of a Human Thrombopoietin-dependent Hematopoietic Cell Line
J. Biol. Chem.,
February 25, 2000;
275(8):
5553 - 5559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Fichelson, J.-M. Freyssinier, F. Picard, M. Fontenay-Roupie, M. Guesnu, M. Cherai, S. Gisselbrecht, and F. Porteu
Megakaryocyte Growth and Development Factor-Induced Proliferation and Differentiation Are Regulated by the Mitogen-Activated Protein Kinase Pathway in Primitive Cord Blood Hematopoietic Progenitors
Blood,
September 1, 1999;
94(5):
1601 - 1613.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Rojnuckarin, J. G. Drachman, and K. Kaushansky
Thrombopoietin-Induced Activation of the Mitogen-Activated Protein Kinase (MAPK) Pathway in Normal Megakaryocytes: Role in Endomitosis
Blood,
August 15, 1999;
94(4):
1273 - 1282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Nagata, N. Takahashi, R. J. Davis, and K. Todokoro
Activation of p38 MAP Kinase and JNK But Not ERK Is Required for Erythropoietin-Induced Erythroid Differentiation
Blood,
September 15, 1998;
92(6):
1859 - 1869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Matsuguchi, M. B. Lilly, and A. S. Kraft
Cytoplasmic Domains of the Human Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF) Receptor beta Chain (hbeta c) Responsible for Human GM-CSF-induced Myeloid Cell Differentiation
J. Biol. Chem.,
July 31, 1998;
273(31):
19411 - 19418.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Matsumura, K. Nakajima, H. Wakao, S. Hattori, K. Hashimoto, H. Sugahara, T. Kato, H. Miyazaki, T. Hirano, and Y. Kanakura
Involvement of Prolonged Ras Activation in Thrombopoietin-Induced Megakaryocytic Differentiation of a Human Factor-Dependent Hematopoietic Cell Line
Mol. Cell. Biol.,
July 1, 1998;
18(7):
4282 - 4290.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Z.-Q. Shi, W. Lu, and G.-S. Feng
The Shp-2 Tyrosine Phosphatase Has Opposite Effects in Mediating the Activation of Extracellular Signal-regulated and c-Jun NH2-terminal Mitogen-activated Protein Kinases
J. Biol. Chem.,
February 27, 1998;
273(9):
4904 - 4908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
