Das P, Maduzia L L, Wang H, Finelli A L, Cho S H, Smith M M, Padgett R W
Waksman Institute, Department of Molecular Biology, Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA.
Development. 1998 Apr;125(8):1519-28. doi: 10.1242/dev.125.8.1519.
Signals from transforming growth factor-beta (TGF-beta) ligands are transmitted within the cell by members of the Smad family, which can be grouped into three classes based on sequence similarities. Our previous identification of both class I and II Smads functioning in a single pathway in C. elegans, raised the issue of whether the requirement for Smads derived from different classes is a general feature of TGF-beta signaling. We report here the identification of a new Drosophila class II Smad, Medea, a close homolog of the human tumor-suppressor gene DPC4. Embryos from germline clones of both Medea and Mad (a class I Smad) are ventralized, as are embryos null for the TGF-beta-like ligand decapentaplegic (dpp). Loss of Medea also blocks dpp signaling during later development, suggesting that Medea, like Mad, is universally required for dpp signaling. Furthermore, we show that the necessity for these two closely related, non-redundant Smads, is due to their different signaling properties - upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus. These results provide a paradigm for, and distinguish between, the requirement for class I and II Smads in Dpp/BMP signaling.
来自转化生长因子-β（TGF-β）配体的信号通过Smad家族成员在细胞内传递，根据序列相似性，Smad家族成员可分为三类。我们之前在秀丽隐杆线虫中鉴定出I类和II类Smad在单一信号通路中发挥作用，这就提出了一个问题，即不同类别的Smad的需求是否是TGF-β信号传导的一个普遍特征。我们在此报告鉴定出一种新的果蝇II类Smad，Medea，它是人类肿瘤抑制基因DPC4的紧密同源物。来自Medea和Mad（一种I类Smad）种系克隆的胚胎均腹化，就像TGF-β样配体“五体不全”（dpp）缺失的胚胎一样。Medea的缺失也会在后期发育过程中阻断dpp信号传导，这表明Medea与Mad一样，是dpp信号传导普遍需要的。此外，我们表明这两种密切相关、不可替代的Smad的必要性，是由于它们不同的信号特性——在Dpp信号通路激活后，需要Mad将Medea主动转运到细胞核中。这些结果为Dpp/BMP信号传导中I类和II类Smad的需求提供了一个范例，并对其进行了区分。
