Unconventional rapid ERK1,2 activation is indispensable for proliferation of the growth factor-independent myeloid leukemic cell line KG1

被引:7
作者
Barge, RMY
Dorrestijn, J
Falkenburg, JHF
Willemze, R
Maassen, JA
机构
[1] Leiden Univ, Dept Hematol, Med Ctr, Leiden, Netherlands
[2] Leiden Univ, Dept Mol Cell Biol, Sect Signal Transduct, Leiden, Netherlands
关键词
myeloid leukemia; signal transduction; Erk kinase;
D O I
10.1038/sj.leu.2400991
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-Erk1,2 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 a 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.
引用
收藏
页码:699 / 704
页数:6
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