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蛋白为一种分泌型形态发生素，对于多种物种和器官的基本发育过程至关重要，包括细胞命运指定、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条：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配体与其受体的结合主要作用是通过抑制β-catenin降解复合物来稳定细胞质中的β-catenin。随后，β-catenin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以及伴随的共激活剂招募，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相关螺旋蛋白激酶1），导致细胞骨架重塑和细胞粘附、运动性变化。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暂时性增加，随后激活蛋白激酶C（PKC）和钙调神经磷酸酶II（CAMKII）以及磷酸酶Calcineurin。资料来源：[http://www.genome.jp/kegg/pathway/hsa/hsa04310.html KEGG]。