Proliferation of human myeloid leukemia cell line associated with the tyrosine-phosphorylation and activation of the proto-oncogene c-kit product.

Proliferation of human myeloid leukemia cell line associated with the tyrosine-phosphorylation and activation of the proto-oncogene c-kit product.
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人骨髓性白血病细胞系的增殖与原癌基因 c-kit 产品的酪氨酸磷酸化和激活相关。

DOI:
10.1182/blood.v78.11.2834.2834
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发表时间:
1991
期刊:
影响因子:
20.3
通讯作者:
Y. Kanayama
Y. Kanayama
中科院分区:
医学1区
文献类型:
--
作者:
A. Kuriu;H. Ikeda;Y. Kanakura;J. Griffin;B. Druker;H. Yagura;H. Kitayama;J. Ishikawa;T. Nishiura;Y. Kanayama

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我们研究了在人因子依赖性髓系白血病细胞系MO 7 E中用c-kit配体刺激前后原癌基因c-kit产物的表达、磷酸化程度和活化。发现含有鼠c-kit产物配体的BALB/3 T3成纤维细胞系的培养上清液以剂量依赖性方式刺激MO 7 E细胞系的增殖。酪氨酸激酶抑制剂genistein可明显抑制细胞增殖。用磷酸酪氨酸特异性单克隆抗体的免疫印迹技术表明,有快速的,剂量依赖性的酪氨酸磷酸化的c-kit产品在响应鼠c-kit配体。此外,鼠c-kit配体在体外增加了c-kit产物的自激酶活性。用人干细胞因子(SCF)(一种用于c-kit产品的重组人配体)获得了类似的结果。这些结果表明,c-kit产物的磷酸化和活化参与了某些人白血病细胞以及正常造血细胞的增殖信号。
We investigated the expression, degree of phosphorylation, and activation of the proto-oncogene c-kit product before and after stimulation with the c-kit ligand in a human factor-dependent myeloid leukemia cell line, MO7E. The culture supernatant of the BALB/3T3 fibroblast cell line, which contains the ligand for the murine c-kit product, was found to stimulate proliferation of the MO7E cell line in a dose-dependent manner. The proliferation was significantly inhibited by a tyrosine kinase inhibitor, genistein. An immunoblot technique with a monoclonal antibody specific for phosphotyrosine, showed that there was rapid, dose-dependent tyrosine-phosphorylation of the c-kit product in response to murine c-kit ligand. Furthermore, the murine c-kit ligand increased autokinase activity of the c-kit product in vitro. Similar results were obtained with human stem cell factor (SCF), a recombinant human ligand for the c-kit product. These results suggest that the phosphorylation and activation of the c-kit product are involved in proliferative signals of some human leukemia cells, as well as of normal hematopoietic cells.
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