一个突变的CSF-1受体的MYC救援受损于mitogenic信号传递
M F Roussel1, J L Cleveland, S A Shurtleff
1Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Nature
|September 26, 1991
概括
殖民地刺激因子-1受体 (CSF-1R) 信号通路分为两部分,氨酸809对c-myc诱导和细胞增殖至关重要. 这突显了c-myc在CSF-1驱动的细胞生长中的核心作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 信号传输 信号传输
背景情况:
- 殖民地刺激因子-1受体 (CSF-1R) 信号传递是复杂的,涉及氨酸激酶活性和细胞内因子.
- 酸化部位附近的特定序列基因介导与细胞质信号分子的相互作用.
研究的目的:
- 研究氨酸809自化部位在CSF-1R信号传递中的作用.
- 阐明下游信号事件,特别是c-myc参与CSF-1诱导的线粒发生.
主要方法:
- 在氨酸809.9的CSF-1R自酸化位点的位点定向突变发生.
- 在无血清介质中培养表达野生型或突变型CSF-1R的NIH3T3细胞.
- 评估细胞增殖,殖民地形成和c-myc mRNA诱导对CSF-1的反应.
主要成果:
- 氨酸809的突变没有显著影响CSF-1R氨酸激酶的活性或与酸丁醇3-激酶的结合.
- 细胞与突变的CSF-1R (Phe 809) 显示受损的增殖和殖民地形成,以应对CSF-1.
- 在突变细胞中,c-myc mRNA的CSF-1诱导显著受损,但可以通过强制c-myc表达来恢复.
结论:
- CSF-1R信号分叉,有不同的途径调节即时的早期基因反应和线粒发生.
- 氨酸809在将CSF-1R激活与c-myc诱导和随后的细胞增殖相结合方面发挥着至关重要的作用.
- c-myc对于CSF-1诱导的线粒发生是必不可少的,它在受体氨酸激酶活性下游起作用.
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