Table 1 The location and function of components in Wnt signaling
Component | Subcellular location | Function |
|---|---|---|
Wnt | Secreted to extracellular matrix | The ligands of the frizzled family, cause activation of TCF/LEF family transcription factors in the canonical Wnt signaling pathways |
Dkk1 | Extracellular region or secreted | Inhibiting the interaction between LRP5/6 and Wnt |
Dkk3 | Extracellular region or secreted | Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt, and promotes internalization of LRP5/6 |
LRP5/6 | Plasma membrane, endoplasmic reticulum, membrane raft | Co-receptor as a member of the frizzled family of seven-transmembrane spanning receptors |
Frizzled | Plasma membrane, endosome | Receptor for Wnt proteins which are coupled to the beta-catenin canonical signaling pathway |
RNF43 | Plasma membrane, endoplasmic reticulum, nucleus | A negative regulator of the Wnt signaling pathway by the ubiquitination, endocytosis, and degradation of Wnt receptor complex components Frizzled |
ZNRF3 | Plasma membrane | A negative regulator of the Wnt signaling pathway by the ubiquitination and degradation of Wnt receptor complex components Frizzled and LRP6 |
Dvl | Cytoplasm and cytosol, plasma membrane, cytoplasmic vesicle | Binding to the frizzled family members and transducing the Wnt signal |
Axin1 | Plasma membrane, cytoplasm and cytosol, nucleus, membrane | Component of the beta-catenin destruction complex that is required for down-regulating beta-catenin levels, modulates Wnt signal and controls dorsoventral patterning, enhances TGF-beta signaling and facilitates the phosphorylation of TP53 |
Axin2 | Cytoplasm and cytosol | Inhibitor of the Wnt signaling pathway by down-regulating beta-catenin |
APC | Plasma membrane, cytoskeleton, golgi apparatus, nucleus | Component of the beta-catenin destruction complex, serves as a negative regulator of Wnt signaling and promotes degradation of beta-catenin, plays a role in hepatocyte growth factor-induced cell migration and the localization of MACF1 to cell membrane |
GSK3 β | Plasma membrane, cytoplasm and cytosol, nucleus | An active protein kinase and component of the beta-catenin destruction complex, phosphorylates the N-terminus of beta-catenin and promotes its degradation |
Tankyrase | Cytoplasm and cytosol, cytoskeleton, golgi apparatus, nucleus, telomere | An activator of Wnt signaling pathway by poly-ADP-ribosylation of Axin1 and Axin2, regulates telomere length and vesicle trafficking |
β-TrCP | Cytoplasm and cytosol, nucleus | Component of the beta-catenin destruction complex and mediates the ubiquitination of beta-catenin |
beta-catenin | Plasma membrane, cytoplasm and cytosol, cytoskeleton, nucleus, adherens junction, cell junction, synapse | beta-catenin accumulates in the nucleus as a coactivator of TCF/LEF family of transcription factors based on the occurrence of Wnt ligands, leading to the activation of Wnt response genes, it is involved in the regulation of cell adhesion, chondrocyte differentiation and centrosome cohesion |
Groucho | Nucleus | Transcriptional corepressor |
TCF1 | Nucleus | Transcriptional activator or repressor, beta-catenin binding, DNA binding |
TCF3 | Nucleus | DNA-binding transcription factor activity, repressing transcription factor binding, bHLH transcription factor binding |
CBP | Cytoplasm and cytosol, nucleus | beta-catenin-TCF complex assembly, acetylates histones and non-histone proteins, specifically binds to phosphorylated CREB and enhances its transcriptional activity, serves as a coactivator or transcriptional coactivator |
Porcupine | Endoplasmic reticulum | palmitoleoyltransferase activity by modifying Wnt protein with the attachment of palmitoleate, a step required for efficient binding to frizzled receptors |