Wnt signaling pathway

Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated coiled-coil-containing protein kinase 1) and leads to remodelling of the cytoskeleton and changes in cell adhesion and motility. WNT-Ca2+ signalling is mediated through G proteins and phospholipases and leads to transient increases in cytoplasmic free calcium that subsequently activate the kinase PKC (protein kinase C) and CAMKII (calcium calmodulin mediated kinase II) and the phosphatase calcineurin. Source: [http://www.genome.jp/kegg/pathway/hsa/hsa04310.html KEGG].

Wnt 蛋白为分泌型形态发生素，在众多物种和器官的基本发育过程中发挥着至关重要的作用，如细胞命运指定、祖细胞增殖以及对非对称细胞分裂的调控。Wnt 信号通路至少包含三种不同的类型：经典通路、平面细胞极性（PCP）通路和 Wnt/Ca2+ 通路。在经典 Wnt 通路中，Wnt 配体与其受体结合的主要作用是通过抑制 β-连环蛋白降解复合物，从而稳定细胞质中的 β-连环蛋白。β-连环蛋白随后得以自由进入细胞核，通过与 TCF（T 细胞因子）家族转录因子相互作用并伴随共激活剂的募集，激活 Wnt 调控基因。平面细胞极性（PCP）信号传导导致小 GTP 酶 RHOA（RAS 同源基因家族成员 A）和 RAC1 的激活，进而激活应激激酶 JNK（Jun N-端激酶）和 ROCK（RHO 相关的卷曲螺旋结构蛋白激酶 1），导致细胞骨架重塑以及细胞粘附和运动的变化。WNT-Ca2+ 信号传导通过 G 蛋白和磷脂酶介导，导致细胞质中游离钙离子的短暂增加，随后激活蛋白激酶 C（PKC）和钙调蛋白依赖性激酶 II（CAMKII）以及磷酸酶钙神经素。资料来源：[http://www.genome.jp/kegg/pathway/hsa/hsa04310.html KEGG]。