一种具有SH2域的新型转化蛋白 (SHC) 涉及到线粒体信号转导
G Pelicci1, L Lanfrancone, F Grignani
1Istituto Clinica Medica I, Policlinico Monteluce, University of Perugia, Italy.
Cell
|July 10, 1992
概括
新发现的SHC蛋白质将激活生长因子受体与细胞增殖途径联系起来. 在小鼠细胞中SHC的过度表达诱导了转变的表型和瘤形成,突出了它在哺乳动物细胞生长调节中的作用.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 在瘤学瘤学.
背景情况:
- 该SHC基因编码了一个包含Src同源2 (SH2) 域的适配蛋白家族.
- SHC蛋白涉及到由生长因子受体启动的信号转导通路.
研究的目的:
- 描述新型SHC基因及其蛋白质产物.
- 研究SHC蛋白在调解激活生长因子受体信号中的作用.
- 为了确定SHC在哺乳动物细胞中的过度表达的功能后果.
主要方法:
- 使用SH2DNA探针进行cDNA库选.
- 使用抗SHC抗体进行西部斑分析.
- 在体外结合测定与细菌表达的SHC SH2域.
- 对NIH 3T3纤维细胞过度表达SHC的表型分析,包括裸体小鼠的瘤形成.
主要成果:
- 隔离和表征SHCcDNA编码46.8和51.7kDa的蛋白质与C端SH2域.
- 在哺乳动物细胞系中识别46,52和66kDa的SHC蛋白.
- 证明SHC蛋白质与活性表皮生长因子受体 (EGFR) 复合并被化.
- 在体外证实了SHC受体协会.
- 在NIH 3T3细胞中构成性SHC过度表达导致了体内转化和瘤形成.
结论:
- SHC基因产物充当关键的中间体,将激活生长因子受体与下游信号通路结合起来.
- SHC蛋白在调节哺乳动物细胞增殖和瘤发生方面发挥着重要作用.
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