Signaling crosstalk between TGFβ and Dishevelled/Par1b.
Signaling crosstalk between TGFβ and Dishevelled/Par1b.
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DOI：
10.1038/cdd.2012.50
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发表时间：
2012-10
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
作者：
信号通路的串扰在后生动物的发育和成年组织的动态平衡过程中是至关重要的。尽管转化生长因子-β(转化生长因子β)转导级联相当简单，但体内对转化生长因子β配体的反应性在几个步骤中受到严格调控。因此，转化生长因子β代表了一个信号系统的活动如何被其他信号系统调节的范例。在这里，我们报告了一个意想不到的调控步骤，涉及蓬乱(DVL)和Par1b(也称为Mark2)。Dv1和Par1b协同作用，使转化生长因子β/骨形态发生蛋白信号在非洲爪哇中胚层发育和转化生长因子β在哺乳动物细胞中的反应性。从机械上讲，Par1b/Dv13/Smad4复合体的组装是由Wnt5a促进的。Smad4与DVL/Par1的结合阻止了它被外胚层蛋白(也称为转录中介因子1伽马或三方基序蛋白33)抑制的泛素化。我们认为这种串扰与协调转化生长因子β反应与WNT非正则通路和极性通路有关。
Crosstalk of signaling pathways is critical during metazoan development and adult tissue homeostasis. Even though the transforming growth factor-beta (TGFβ) transduction cascade is rather simple, in vivo responsiveness to TGFβ ligands is tightly regulated at several steps. As such, TGFβ represents a paradigm for how the activity of one signaling system is modulated by others. Here, we report an unsuspected regulatory step involving Dishevelled (Dvl) and Par1b (also known as MARK2). Dvl and Par1b cooperate to enable TGFβ/bone morphogenetic protein (BMP) signaling in Xenopus mesoderm development and TGFβ responsiveness in mammalian cells. Mechanistically, the assembly of the Par1b/Dvl3/Smad4 complex is fostered by Wnt5a. The association of Smad4 to Dvl/Par1 prevents its inhibitory ubiquitination by ectodermin (also known as transcriptional intermediary factor 1 gamma or tripartite motif protein 33). We propose that this crosstalk is relevant to coordinate TGFβ responses with Wnt-noncanonical and polarity pathways.
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影响因子：
13
作者：
Eivers, Edward;Demagny, Hadrien;De Robertis, E. M.
通讯作者：
De Robertis, E. M.
影响因子：
11.4
作者：
Kusakabe, M;Nishida, E
通讯作者：
Nishida, E
影响因子：
11.8
作者：
Oelgeschläger, M;Kuroda, H;De Robertis, EM
通讯作者：
De Robertis, EM
影响因子：
64.5
作者：
Dupont, Sirio;Mamidi, Anant;Piccolo, Stefano
通讯作者：
Piccolo, Stefano
影响因子：
9.2
作者：
Park, TJ;Gray, RS;Wallingford, JB
通讯作者：
Wallingford, JB