Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signaling pathway in endothelial cells. Can also amplify Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3.

1. These results shed new light on the role of Rspo3 in heart development and demonstrate that LGR4 is the principal R-spondin 3 receptor in the heart. PMID: 29859889
2. Results identify a mechanism through which localized expression of RSPO3 induces proliferation of the coronary arteries at their stems and permits their formation. PMID: 28834739
3. Rspo3-LGR4 axis protects hepatocytes from hypoxia/reoxygenation injury via activating beta-catenin. PMID: 29555474
4. H. pylori infection increases stromal R-spondin 3 expression and expands the Axin2(+) cell pool to cause hyperproliferation and gland hyperplasia; the ability of stromal niche cells to control and adapt epithelial stem cell dynamics constitutes a sophisticated mechanism that orchestrates epithelial regeneration and maintenance of tissue integrity PMID: 28813421
5. We provide in vivo evidence that RSPO3 stimulates the crypt stem cell and niche compartments and drives rapid intestinal tumorigenesis. PMID: 27511199
6. Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa PMID: 27313319
7. Conditional deletion of Rspo3 in mice disrupts activation of central fate, demonstrating its crucial role in determining and maintaining beta-catenin-dependent zonation. PMID: 26655896
8. data identify endothelial RSPO3-driven non-canonical WNT/Ca(2+)/NFAT signaling as a critical maintenance pathway of the remodeling vasculature PMID: 26766444
9. Nkx2-5 has a role in regulating cardiac growth through modulation of Wnt signaling by R-spondin3 PMID: 25053429
10. Rspo3 loss of function mutation in combination with Rspo2 mutation,but not on its own, causes severe limb truncation. PMID: 22610508
11. Sexually dimorphic expression patterns were observed for WNT/beta-catenin-responsive genes, and for Wnt2b, Wnt4, Wnt7a, Wnt9b, Wnt10b, Wnt11, Wnt16, and Rspo3 mRNAs. PMID: 21936019
12. Data show that Rspo3 binds syndecan 4 and that together they activate Wnt5a/PCP signaling. PMID: 21397842
13. suggest a critical role for Rspo3 in the interaction between chorion and allantois in labyrinthine development PMID: 16963017
14. identify Rspo3 as a novel, evolutionarily conserved angiogenic factor in embryogenesis PMID: 18842812

顯示更多

收起更多

Secreted.

R-spondin family

Highly expressed in endothelial cells.

KEGG: mmu:72780

STRING: 10090.ENSMUSP00000090287

UniGene: Mm.45191