Abstract
While normal hematopoietic progenitor cells are dependent on colony-stimulating factors for in vitro proliferation, myeloid leukemic cells are frequently factor-independent. In this study we investigated several signalling intermediates of the Ras-Er1,2 pathway which may be involved in the development of growth factor independence. In the growth factor independent cell line KG1, an extremely short activation pattern of Erk1,2 with a maximum at 30 s was observed in response to FBS. In contrast, stimulation of the IL-3 receptor in AML193 cells resulted in a transient Erk activation peaking at 5 min and returning to base levels after 15 min. Although the Erk activation in KG1 cells is short-lived, using the MEK inhibitor PD98059, we demonstrated that Erk phosphorylation is essential for proliferation of these cell lines. We also detected major differences in Shc phosphorylation between factor-dependent and -independent cells. These data suggest that Erk activation is essential for proliferation of growth factor-dependent and -independent leukemic cells. The minimal Erk activation observed in KG1 cells in response to serum is sufficient for mitogenesis of these cells.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing*
-
Adaptor Proteins, Vesicular Transport*
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
-
Cell Division / physiology
-
Enzyme Activation
-
Enzyme Inhibitors / pharmacology
-
Flavonoids / pharmacology
-
Humans
-
Interleukin-3 / pharmacology*
-
Interleukin-3 / physiology
-
Leukemia, Myeloid / enzymology*
-
Leukemia, Myeloid / pathology*
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinases*
-
Phosphorylation
-
Protein Kinase C / deficiency
-
Protein Kinase C / metabolism
-
Proteins / metabolism
-
Shc Signaling Adaptor Proteins
-
Signal Transduction / physiology
-
Src Homology 2 Domain-Containing, Transforming Protein 1
-
Tumor Cells, Cultured
-
ras Proteins / biosynthesis
-
ras Proteins / physiology
Substances
-
Adaptor Proteins, Signal Transducing
-
Adaptor Proteins, Vesicular Transport
-
Enzyme Inhibitors
-
Flavonoids
-
Interleukin-3
-
Proteins
-
SHC1 protein, human
-
Shc Signaling Adaptor Proteins
-
Src Homology 2 Domain-Containing, Transforming Protein 1
-
Protein Kinase C
-
Calcium-Calmodulin-Dependent Protein Kinases
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinases
-
ras Proteins
-
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one