Bergmann A, Agapite J, McCall K, Steller H
Massachusetts Institute of Technology, Howard Hughes Medical Institute, Department of Biology, Cambridge 02139, USA.
Cell. 1998 Oct 30;95(3):331-41. doi: 10.1016/s0092-8674(00)81765-1.
Extracellular growth factors are required for the survival of most animal cells. They often signal through the activation of the Ras pathway. However, the molecular mechanisms by which Ras signaling inhibits the intrinsic cell death machinery are not well understood. Here, we present evidence that in Drosophila, activation of the Ras pathway specifically inhibits the proapoptotic activity of the gene head involution defective (hid). By using transgenic animals and cultured cells, we show that MAPK phosphorylation sites in Hid are critical for this response. These findings define a novel mechanism by which growth factor signaling directly inactivates a critical component of the intrinsic cell death machinery. These studies provide further insights into the function of ras as an oncogene.
大多数动物细胞的存活需要细胞外生长因子。它们通常通过激活Ras信号通路来传递信号。然而，Ras信号传导抑制细胞内在死亡机制的分子机制尚未完全明确。在此，我们提供证据表明，在果蝇中，Ras信号通路的激活特异性地抑制了促凋亡基因头部内卷缺陷（hid）的活性。通过使用转基因动物和培养细胞，我们表明Hid中的MAPK磷酸化位点对此反应至关重要。这些发现定义了一种新机制，即生长因子信号传导直接使细胞内在死亡机制的关键组分失活。这些研究为Ras作为癌基因的功能提供了进一步的见解。
