LeMosy E K, Tan Y Q, Hashimoto C
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5055-60. doi: 10.1073/pnas.081026598. Epub 2001 Apr 10.
Dorsoventral patterning of the Drosophila embryo is initiated by a ventralizing signal. Production of this signal requires the serine proteases Gastrulation Defective (GD), Snake, and Easter, which genetic studies suggest act sequentially in a cascade that is activated locally in response to a ventral cue provided by the pipe gene. Here, we demonstrate biochemically that GD activates Snake, which in turn activates Easter. We also provide evidence that GD zymogen cleavage is important for triggering this cascade but is not spatially localized by pipe. Our results suggest that a broadly, rather than locally, activated protease cascade produces the ventralizing signal, so a distinct downstream step in this cascade must be spatially regulated to restrict signaling to the ventral side of the embryo.
果蝇胚胎的背腹模式形成是由一种腹侧化信号启动的。这种信号的产生需要丝氨酸蛋白酶原肠胚形成缺陷(GD)、蛇蛋白和伊斯特蛋白,遗传学研究表明它们在一个级联反应中依次起作用,该级联反应是响应由管道基因提供的腹侧信号而在局部被激活的。在这里,我们通过生化实验证明GD激活蛇蛋白,而蛇蛋白又激活伊斯特蛋白。我们还提供证据表明,GD酶原的切割对于触发这一级联反应很重要,但不受管道基因的空间定位影响。我们的结果表明,一个广泛而非局部激活的蛋白酶级联反应产生了腹侧化信号,因此该级联反应中一个独特的下游步骤必须在空间上受到调控,以将信号传导限制在胚胎的腹侧。