通过膜的TGF-α前体激活了EGF/TGF-α受体
R Brachmann1, P B Lindquist, M Nagashima
1Department of Developmental Biology, Genentech, Inc., South San Francisco, California 94080.
Cell
|February 24, 1989
概括
超膜转化生长因子-α (TGF-alpha) 前体形式激活表皮生长因子 (EGF) 受体. 这些与膜结合的TGF-α形式促进细胞生长,并可能在增殖组织中的细胞间通信中发挥作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子信号传递是分子信号传递.
- 癌症研究 癌症研究
背景情况:
- 转化生长因子-α (TGF-α) 和表皮生长因子 (EGF) 是相关的生长因子,激活一个共同的受体.
- 蛋白质分解裂解释放出可溶性TGF-alpha,但膜结合的形式也存在于细胞表面.
研究的目的:
- 为了研究与膜结合的TGF-α前体形式的生物活性.
- 要确定这些形式是否可以激活EGF/TGF-α受体并影响细胞增殖.
主要方法:
- 对TGF-alpha前体进行基因改造,以防止裂变.
- 在受体阴性细胞中转基因cDNA的过度表达.
- 部分净化和TGF-α形式的N-终端测序.
- 检测受体自化和结独立细胞生长.
主要成果:
- 确定了两种跨膜TGF-α前体形式.
- 这些形式诱导了受体过表达细胞中EGF/TGF-α受体的氨酸自酸化.
- 溶解的前体促进了纤维细胞的独立于 anchorage 的生长.
- 细胞与细胞的接触也导致了受体激活.
结论:
- 跨膜TGF-α前体形式具有生物活性.
- 它们可以激活EGF/TGF-α受体并刺激细胞增殖.
- 这些发现表明,膜结合的TGF-alpha在增殖组织中的细胞相互作用中起着作用.
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