Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways
Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways
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DOI：
10.1038/383832a0
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发表时间：
1996-10-31
期刊：
影响因子：
64.8
通讯作者：
Massague, J
中科院分区：
文献类型：
--
作者：
Lagna, G;Hata, A;Massague, J
tgf - β /激活素/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质受体复合物发出信号(1)tgf - β样分子产生的信号似乎由一组进化上保守的被称为SMAD的蛋白质转导，这些蛋白质在激活后直接转运到细胞核，在那里它们可能激活转录(2)。迄今为止，在脊椎动物中已经鉴定了五种SMAD蛋白(1)。这些因素与果蝇的十肢截瘫（dpp）信号传导介质、母体对抗dpp （Mad）有关(3)，也与秀丽隐杆线虫的Sma基因有关(4)。Smad1和Smad2分别在爪蟾和哺乳动物细胞中模拟BMP和激活素的作用（2,5-9），而Smad3 （Smad2的近亲）和相关蛋白DPC4（一种肿瘤抑制基因产物）介导tgf - β的作用（11）。我们在这里报道，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通路中的功能以及乳腺上皮细胞的抗丝原性和转录反应至关重要，DPC4与Smad1在响应BMP和Smad2在响应激活素或tgf - β时相关联。因此，DPC4是在tgf - β家族的不同信号通路中起作用的smad的调控伙伴。
THE TGF-beta/activin/BMP superfamily of growth factors signals through heteromeric receptor complexes of type I and type II serine/threonine kinase receptors(1) 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(2), Five SMAD proteins have so far been characterized in vertebrates(1), These factors are related to the mediator of decapentaplegic (dpp) signalling, mothers against dpp (Mad), in Drosophila(3) and to the Sma genes from Caenorhabditis elegans(4). Smad1 and Smad2 have been shown to mimic the effects of BMP and activin, respectively, both in Xenopus and in mammalian cells(2,5-9), whereas Smad3 (a close homologue of Smad2) and the related protein DPC4, a tumour-suppressor gene product(10), mediate TGF-beta actions(11). 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.