Park W Y, Ahn J H, Feldman R A, Seo J S
Ilchun Institute for Molecular Medicine and Department of Biochemistry, Seoul National University College of Medicine, South Korea.
Cancer Lett. 1998 Jul 3;129(1):29-37. doi: 10.1016/s0304-3835(98)00077-9.
Granulocyte-macrophage colony stimulating factor (GM-CSF) induces proliferation and maturation of myeloid progenitor cells and also activates neutrophils. In order to investigate the pleiotropic effects of GM-CSF stimulation, we examined the signaling pathways of protein tyrosine kinases (PTKs) and signal transducers and activators of transcription (STATs) in GM-CSF-dependent proliferation of leukemia cells. Using TF-1, a GM-CSF-dependent human erythroleukemia cell line, we found that GM-CSF enhanced DNA-binding and tyrosine phosphorylation of STAT3. GM-CSF receptor (GM-CSFR) and c-Fes tyrosine kinase were also activated upon GM-CSF stimulation. Furthermore, c-Fes formed a complex with STAT3. Experiments using a c-Fes mutant that lacked tyrosine kinase activity revealed that the activation of STAT3 is kinase-dependent, but that the c-Fes-STAT3 interaction is not affected by c-Fes tyrosine kinase activity. The results suggest that STAT3 is activated by c-Fes tyrosine kinase through direct interaction during hematopoietic cell proliferation induced by GM-CSF.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）可诱导髓系祖细胞增殖和成熟，还能激活中性粒细胞。为了研究GM-CSF刺激的多效性作用，我们检测了白血病细胞依赖GM-CSF增殖过程中蛋白酪氨酸激酶（PTK）和信号转导及转录激活因子（STAT）的信号通路。利用TF-1，一种依赖GM-CSF的人红白血病细胞系，我们发现GM-CSF增强了STAT3的DNA结合及酪氨酸磷酸化。GM-CSF受体（GM-CSFR）和c-Fes酪氨酸激酶在GM-CSF刺激后也被激活。此外，c-Fes与STAT3形成复合物。使用缺乏酪氨酸激酶活性的c-Fes突变体进行的实验表明，STAT3的激活依赖激酶，但c-Fes与STAT3的相互作用不受c-Fes酪氨酸激酶活性的影响。结果提示，在GM-CSF诱导的造血细胞增殖过程中，STAT3通过与c-Fes酪氨酸激酶直接相互作用而被激活。
