|ZFIN ID: ZDB-PUB-080908-2|
Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation
Ding, Y., Xi, Y., Chen, T., Wang, J.Y., Tao, D.L., Wu, Z.L., Li, Y.P., Li, C., Zeng, R., and Li, L.
|Source:||The Journal of cell biology 182(5): 865-872 (Journal)|
|Registered Authors:||Li, Lin|
|PubMed:||18762581 Full text @ J. Cell Biol.|
Ding, Y., Xi, Y., Chen, T., Wang, J.Y., Tao, D.L., Wu, Z.L., Li, Y.P., Li, C., Zeng, R., and Li, L. (2008) Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation. The Journal of cell biology. 182(5):865-872.
ABSTRACTThe low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are coreceptors for Frizzled and transmit signals from the plasma membrane to the cytosol. However, the mechanism for LRP5/6 signal transmission remains undefined. Here, we identify cytoplasmic activation/proliferation-associated protein 2 (Caprin-2) as a LRP5/6-binding protein. Our data show that Caprin-2 stabilizes cytosolic beta-catenin and enhances lymphoid enhancer-binding factor 1/T cell factor-dependent reporter gene activity as well as the expression of Wnt target genes in mammalian cells. Morpholino-mediated knockdown of Caprin-2 in zebrafish embryos inhibits Wnt/beta-catenin signaling and results in a dorsalized phenotype. Moreover, Caprin-2 facilitates LRP5/6 phosphorylation by glycogen synthase kinase 3, and thus enhances the interaction between Axin and LRP5/6. Therefore, Caprin-2 promotes activation of the canonical Wnt signaling pathway by regulating LRP5/6 phosphorylation.