non-canonical Wnt signaling pathway
Definition
Target type: biologicalprocess
A type of Wnt signaling pathway in which Wnt binding to its receptor on the surface of a target cell results in the by propagation of the molecular signals via effectors other than beta-catenin. [PMID:37804416]
The non-canonical Wnt signaling pathway, unlike the canonical Wnt pathway, does not involve β-catenin accumulation and activation of TCF/LEF transcription factors. Instead, it primarily functions through two distinct branches: the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway.
The PCP pathway, mediated by Wnt5a, Wnt11, and other Wnt ligands, regulates cell polarity and tissue organization during development. It involves the activation of Dishevelled (Dvl), which then interacts with a complex of proteins including Frizzled receptors, Vangl, and Prickle, to regulate cytoskeletal rearrangements and cell movements. This pathway plays a crucial role in establishing tissue polarity, cell migration, and organogenesis.
The Wnt/Ca2+ pathway, triggered by Wnt5a, Wnt11, and other Wnt ligands, regulates calcium signaling and downstream gene expression. It involves the activation of G proteins, which stimulate phospholipase C (PLC) to produce diacylglycerol (DAG) and inositol trisphosphate (IP3). IP3 mobilizes intracellular calcium, leading to the activation of protein kinase C (PKC) and other calcium-dependent signaling molecules. This pathway participates in cell proliferation, apoptosis, and other cellular processes.
Both the PCP and Wnt/Ca2+ pathways, although distinct, can converge and interact. For instance, calcium signaling can influence PCP signaling, and PCP components can modulate calcium levels.
Overall, the non-canonical Wnt signaling pathway plays a crucial role in various developmental and cellular processes, contributing to tissue morphogenesis, cell fate determination, and cellular responses to external cues. Its deregulation is implicated in several diseases, including cancer and developmental disorders.'
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Proteins (3)
| Protein | Definition | Taxonomy |
|---|---|---|
| Secreted frizzled-related protein 1 | A secreted frizzled-related protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N474] | Homo sapiens (human) |
| Myocilin | A myocilin that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q99972] | Homo sapiens (human) |
| Protein Wnt-3a | A protein Wnt-3a that is encoded in the genome of human. [PRO:DNx, UniProtKB:P56704] | Homo sapiens (human) |
Compounds (9)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 4-[(2,4,6-triamino-5-pyrimidinyl)azo]benzoic acid | benzoic acids | ||
| 1-(4-hydroxyphenyl)-3-(3-methoxyphenyl)thiourea | thioureas | ||
| apigenin | Chamomile: Common name for several daisy-like plants (MATRICARIA; TRIPLEUROSPERMUM; ANTHEMIS; CHAMAEMELUM) native to Europe and Western Asia, now naturalized in the United States and Australia. | trihydroxyflavone | antineoplastic agent; metabolite |
| 2',3,4-trihydroxychalcone | 2',3,4-trihydroxychalcone: structure given in first source | catechols; chalcones | |
| gw-5074 | |||
| 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 |
| CCT251545 | CCT251545 : A chloropyridine that is 3-chloropyridine substituted by a 1-oxo-2,8-diazaspiro[4.5]decan-8-yl group and a 4-(1-methyl-1H-pyrazol-4-yl)phenyl group at positions 4 and 5, respectively. It is an orally bioavailable inhibitor of Wnt signaling (IC50 = 5 nM) and a potent and selective chemical probe for cyclin-dependent kinases CDK8 and CDK19. CCT251545: a Wnt signaling inhibitor; structure in first source | azaspiro compound; chloropyridine; pyrazoles | antineoplastic agent; EC 2.7.11.22 (cyclin-dependent kinase) inhibitor; Wnt signalling inhibitor |
| xav939 | XAV939 : A thiopyranopyrimidine in which a 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine skeleton is substituted at C-4 by a hydroxy group and at C-2 by a para-(trifluoromethyl)phenyl group. XAV939: selectively inhibits beta-catenin-mediated transcription; structure in first source | (trifluoromethyl)benzenes; thiopyranopyrimidine | tankyrase inhibitor |
| nvp-tnks656 |