Abstract
Human hematopoietic progenitor cells (TF-1) undergo apoptosis upon deprivation of their dependent cytokine. In this report, we have isolated and characterized some spontaneously derived cytokine-independent variants from TF-1 cells. Analysis of several signaling molecules known to be activated by the GM-CSF pathway revealed that two non-autocrine variants were still responsive to GM-CSF stimulation. However, both variants, without ligand stimulation, already had some activated forms of Raf and MAP kinases. Given current knowledge, the activated Raf/MAP kinase pathway was likely to be responsible for the survival of both variants in the cytokine-free medium. However, the growth of hybrids between wild type and either variant was unexpectedly dependent on GM-CSF. Both variants like the wild type cells were still susceptible to apoptosis induced by other stimuli. These results suggest that either the activated Raf/MAP kinase pathway in both variants is not sufficient to repress the 'two-fold' death signals generated from the hybrids or that there is another mechanism that is responsible for the factor-independent growth of both variants.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Apoptosis / physiology
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / physiology*
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Cell Division / drug effects
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Cell Division / physiology
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Cells, Cultured
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Enzyme Activation
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Granulocyte-Macrophage Colony-Stimulating Factor / deficiency
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
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Granulocyte-Macrophage Colony-Stimulating Factor / physiology
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / drug effects*
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Hematopoietic Stem Cells / physiology
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Humans
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Interleukin-3 / deficiency
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Interleukin-3 / pharmacology
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Interleukin-3 / physiology
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Protein Serine-Threonine Kinases / metabolism
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Protein Serine-Threonine Kinases / physiology*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-raf
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Signal Transduction / physiology*
Substances
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Interleukin-3
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Proto-Oncogene Proteins
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Granulocyte-Macrophage Colony-Stimulating Factor
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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Calcium-Calmodulin-Dependent Protein Kinases