Lagna G, Hata A, Hemmati-Brivanlou A, Massagué J
Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Nature. 1996 Oct 31;383(6603):832-6. doi: 10.1038/383832a0.
The TGF-beta/activin/BMP superfamily of growth factors signals through heteromeric receptor complexes of type I and type II serine/threonine kinase receptors. The signal originated by TGF-beta-like molecules appears to be transduced by a set of evolutionarily conserved proteins known as SMADs, which upon activation directly translocate to the nucleus where they may activate transcription. Five SMAD proteins have so far been characterized in vertebrates. These factors are related to the mediator of decapentaplegic (dpp) signalling, mothers against dpp (Mad), in Drosophila and to the Sma genes from Caenorhabditis elegans. Smad1 and Smad2 have been shown to mimic the effects of BMP and activin, respectively, both in Xenopus and in mammalian cells, whereas Smad3 (a close homologue of Smad2) and the related protein DPC4, a tumour-suppressor gene product, mediate TGF-beta actions. We report here that DPC4 is essential for the function of Smad1 and Smad2 in pathways that signal mesoderm induction and patterning in Xenopus embryos, as well as antimitogenic and transcriptional responses in breast epithelial cells. DPC4 associates with Smad1 in response to BMP and with Smad2 in response to activin or TGF-beta. DPC4 is therefore a regulated partner of SMADs that function in different signalling pathways of the TGF-beta family.
转化生长因子-β/激活素/骨形态发生蛋白（TGF-β/activin/BMP）生长因子超家族通过I型和II型丝氨酸/苏氨酸激酶受体的异源二聚体复合物发出信号。由TGF-β样分子产生的信号似乎由一组被称为SMAD的进化保守蛋白转导，这些蛋白在激活后直接转运到细胞核，在那里它们可能激活转录。到目前为止，在脊椎动物中已鉴定出五种SMAD蛋白。这些因子与果蝇中脱尾蛋白（dpp）信号传导的介质、抗dpp（Mad）的母体以及秀丽隐杆线虫的Sma基因有关。已证明Smad1和Smad2分别在非洲爪蟾和哺乳动物细胞中模拟骨形态发生蛋白（BMP）和激活素的作用，而Smad3（Smad2的紧密同源物）和相关蛋白DPC4（一种肿瘤抑制基因产物）介导TGF-β的作用。我们在此报告，DPC4对于Smad1和Smad2在非洲爪蟾胚胎中中胚层诱导和模式形成信号传导途径以及乳腺上皮细胞中的抗有丝分裂和转录反应的功能至关重要。DPC4在响应BMP时与Smad1结合，在响应激活素或TGF-β时与Smad2结合。因此，DPC4是在TGF-β家族不同信号传导途径中起作用的SMAD的调节伙伴。
