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Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation.


ABSTRACT: The 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.

SUBMITTER: Ding Y 

PROVIDER: S-EPMC2528581 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation.

Ding Yu Y   Xi Ying Y   Chen Ting T   Wang Ji-yong JY   Tao Dong-lei DL   Wu Zhi-Li ZL   Li Yi-ping YP   Li Chen C   Zeng Rong R   Li Lin L  

The Journal of cell biology 20080901 5


The 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 a  ...[more]

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