Mellitzer G, Wessely O, Decker T, Meinke A, Hayman M J, Beug H
Institute of Molecular Pathology, Vienna, Austria.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9600-5. doi: 10.1073/pnas.93.18.9600.
Self renewal of normal erythroid progenitors is induced by the receptor tyrosine kinase c-ErbB, whereas other receptors (c-Kit/Epo-R) regulate erythroid differentiation. To address possible mechanisms that could explain this selective activity of c-ErbB, we analyzed the ability of these receptors to activate the different members of the Stat transcription factor family. Ligand activation of c-ErbB induced the tyrosine phosphorylation, DNA-binding, and reporter gene transcription of Stat 5b in erythroblasts. In contrast, ligand activation of c-Kit was unable to induce any of these effects in the same cells. Activation of the erythropoietin receptor caused specific DNA-binding of Stat 5b, but failed to induce reporter gene transcription. These biochemical findings correlate perfectly with the selective ability of c-ErbB to cause sustained self renewal in erythroid progenitors.
正常红系祖细胞的自我更新由受体酪氨酸激酶c-ErbB诱导，而其他受体（c-Kit/Epo-R）则调节红系分化。为了探究可能解释c-ErbB这种选择性活性的机制，我们分析了这些受体激活Stat转录因子家族不同成员的能力。c-ErbB的配体激活诱导了成红细胞中Stat 5b的酪氨酸磷酸化、DNA结合及报告基因转录。相反，c-Kit的配体激活在相同细胞中无法诱导这些效应中的任何一种。促红细胞生成素受体的激活导致了Stat 5b的特异性DNA结合，但未能诱导报告基因转录。这些生化结果与c-ErbB在红系祖细胞中引起持续自我更新的选择性能力完美相关。
