canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation
Definition
Target type: biologicalprocess
The series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes involved in mesenchymal stem cell differentiation. [GOC:BHF, GOC:jl]
The canonical Wnt signaling pathway plays a crucial role in mesenchymal stem cell (MSC) differentiation, orchestrating a complex cascade of events that ultimately determines the fate of these pluripotent cells. This pathway is initiated by the binding of Wnt proteins, secreted signaling molecules, to their cognate receptors, Frizzled (Fzd) proteins, located on the cell surface. This interaction triggers a signaling cascade involving the recruitment of Dishevelled (Dvl) proteins, which in turn inhibits the formation of a protein complex containing Axin, Adenomatous polyposis coli (APC), and glycogen synthase kinase 3 beta (GSK3β). This complex normally targets β-catenin for phosphorylation, leading to its degradation by the proteasome. However, in the presence of Wnt, Dvl disrupts the formation of this complex, stabilizing β-catenin and allowing it to accumulate in the cytoplasm. β-catenin then translocates to the nucleus, where it interacts with T cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors, forming a complex that activates the transcription of target genes involved in MSC differentiation. These target genes include genes involved in cell proliferation, survival, and the commitment to specific lineages, including osteoblasts, chondrocytes, adipocytes, and myoblasts. The precise lineage specification is influenced by the interplay of Wnt signaling with other signaling pathways and the cellular microenvironment. In the absence of Wnt, the canonical Wnt signaling pathway is inactive, and β-catenin is degraded, preventing the activation of Wnt target genes and promoting a quiescent state in MSCs. This dynamic interplay between Wnt signaling and other factors, including growth factors, cytokines, and extracellular matrix components, ultimately controls the fate of MSCs, enabling them to differentiate into various cell types and contribute to tissue regeneration and repair.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Proto-oncogene Wnt-3 | A proto-oncogene Wnt-3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P56703] | Homo sapiens (human) |
| Catenin beta-1 | A catenin beta-1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P35222] | Homo sapiens (human) |
Compounds (8)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| salvin | salvin: a biocyclic diterpenoid; from sage and rosemary (Lamiaceae) | abietane diterpenoid; carbotricyclic compound; catechols; monocarboxylic acid | angiogenesis modulating agent; anti-inflammatory agent; antineoplastic agent; antioxidant; apoptosis inducer; food preservative; HIV protease inhibitor; plant metabolite |
| toxoflavin | toxoflavin : A pyrimidotriazine that is 1,6-dimethyl-1,5,6,7-tetrahydropyrimido[5,4-e][1,2,4]triazine with oxo groups at positions 5 and 7. toxoflavin: azapteridine antibiotic; structure | carbonyl compound; pyrimidotriazine | antibacterial agent; antineoplastic agent; apoptosis inducer; bacterial metabolite; toxin; virulence factor; Wnt signalling inhibitor |
| cercosporin | cercosporin : An organic heterohexacyclic compound that is perylo[1,12-def][1,3]dioxepine-6,11-dione substituted by hydroxy groups at positions 5 and 12, by methoxy groups at positions 7 and 10, and by 2-hydroxypropyl groups at positions 8 and 9 (the R,R-stereoisomer). It is a phytotoxin which was first isolated from the pathogenic soybean fungus, Cercospora kikuchii and later found in multiple members of the genus Cercospora. cercosporin: phyytotoxin from Cercospora beticola Sacc; posses photodynamic action on mice, bacteria & plants | ||
| LSM-42773 | aromatic ketone | ||
| etodolac, (-)-isomer | (R)-etodolac : The R-enantiomer of etodolac. It is inactive, in contrast to the enantiomer, (S)-etodolac, which is a preferential inhibitor of cyclo-oxygenase 2 and a non-steroidal anti-inflammatory. The racemate is commonly used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain. | etodolac | |
| iwr-1 exo | IWR-1-exo : A dicarboximide having an exo bridged phthalimide structure, substituted at nitrogen by a 4-(quinolin-8-ylcarbamoyl)benzoyl group. It is a weak axin stabilizer, an analogue of IWR-1-endo. | bridged compound; dicarboximide | axin stabilizer |
| ucn 1028 c | calphostin C: structure given in first source; isolated from Cladosporium cladosporioides | ||
| WAY-316606 | WAY-316606 : A sulfonamide resulting from the formal condensation of the sulfonic acid group of 5-(phenylsulfonyl)-2-(trifluoromethyl)benzenesulfonic acid with the primary amino group of piperidin-4-amine. An inhibitor of secreted Frizzled-Related Protein-1 (sFRP-1). | (trifluoromethyl)benzenes; piperidines; secondary amino compound; sulfonamide; sulfone | secreted frizzled-related protein 1 inhibitor |