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, Terry Vik

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

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 bematopoietic 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.

Original languageEnglish
Pages (from-to)3462-3470
Number of pages9
JournalBlood
Volume90
Issue number9
StatePublished - 1997

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Mitogen-Activated Protein Kinases
Cell Differentiation
Chemical activation
Phosphotransferases
Mitogen-Activated Protein Kinase Kinases
Cells
Stem Cell Factor
Cell Line
Electroporation
Growth and Development
Cell proliferation
Transfection
Complementary DNA
Clone Cells
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • Hematology

Cite this

Activation of the mitogen-activated protein kinase pathway is involved in and sufficient for megakaryocytic differentiation of CMK cells. / Melemed, Allen S.; Ryder, John W.; Vik, Terry.

In: Blood, Vol. 90, No. 9, 1997, p. 3462-3470.

Research output: Contribution to journalArticle

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