NODAL 信号传导
中文名称
通路描述
NODAL 信号传导对于胚胎轴的分化和中胚层及内胚层的形成至关重要（参见 Schier 2009, Shen 2007）。NODAL 前蛋白被分泌并细胞外切割以产生成熟的 NODAL。成熟的 NODAL 同源二聚化，并与 LEFTY1、LEFTY2 或 CERBERUS 形成异源二聚体，从而负向调节 NODAL 信号传导。NODAL 也与 GDF1 形成异源二聚体，增加 NODAL 活性。NODAL 二聚体结合 NODAL 受体，该受体包含一种 I 型激活受体（ACVR1B 或 ACVR1C）、一种 II 型激活受体（ACVR2A 或 ACVR2B）和 EGF-CFC 核心受体（CRIPTO 或 CRYPTIC）。结合 NODAL 后，II 型激活受体磷酸化 I 型激活受体，然后磷酸化 SMAD2 和 SMAD3（R-SMADs）。磷酸化的 SMAD2 和 SMAD3 与 SMAD4（CO-SMAD）形成异源寡聚复合物，并转运至细胞核。在细胞核内，SMAD 复合物与转录因子（如 FOXH1）相互作用，激活靶基因的转录。
英文描述
Signaling by NODAL Signaling by NODAL is essential for patterning of the axes of the embryo and formation of mesoderm and endoderm (reviewed in Schier 2009, Shen 2007). The NODAL proprotein is secreted and cleaved extracellularly to yield mature NODAL. Mature NODAL homodimerizes and can also form heterodimers with LEFTY1, LEFTY2, or CERBERUS, which negatively regulate NODAL signaling. NODAL also forms heterodimers with GDF1, which increases NODAL activity. NODAL dimers bind the NODAL receptor comprising a type I Activin receptor (ACVR1B or ACVR1C), a type II Activin receptor (ACVR2A or ACVR2B), and an EGF-CFC coreceptor (CRIPTO or CRYPTIC). After binding NODAL, the type II activin receptor phosphorylates the type I activin receptor which then phosphorylates SMAD2 and SMAD3 (R-SMADs). Phosphorylated SMAD2 and SMAD3 form hetero-oligomeric complexes with SMAD4 (CO-SMAD) and transit from the cytosol to the nucleus. Within the nucleus the SMAD complexes interact with transcription factors such as FOXH1 to activate transcription of target genes.
所含基因
22 个基因