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

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...

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Autores principales: Ding, Yu, Xi, Ying, Chen, Ting, Wang, Ji-yong, Tao, Dong-lei, Wu, Zhi-Li, Li, Yi-ping, Li, Chen, Zeng, Rong, Li, Lin
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528581/
https://www.ncbi.nlm.nih.gov/pubmed/18762581
http://dx.doi.org/10.1083/jcb.200803147
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author Ding, Yu
Xi, Ying
Chen, Ting
Wang, Ji-yong
Tao, Dong-lei
Wu, Zhi-Li
Li, Yi-ping
Li, Chen
Zeng, Rong
Li, Lin
author_facet Ding, Yu
Xi, Ying
Chen, Ting
Wang, Ji-yong
Tao, Dong-lei
Wu, Zhi-Li
Li, Yi-ping
Li, Chen
Zeng, Rong
Li, Lin
author_sort Ding, Yu
collection PubMed
description 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 β-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/β-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.
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spelling pubmed-25285812009-03-08 Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation Ding, Yu Xi, Ying Chen, Ting Wang, Ji-yong Tao, Dong-lei Wu, Zhi-Li Li, Yi-ping Li, Chen Zeng, Rong Li, Lin J Cell Biol Research Articles 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 β-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/β-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. The Rockefeller University Press 2008-09-08 /pmc/articles/PMC2528581/ /pubmed/18762581 http://dx.doi.org/10.1083/jcb.200803147 Text en © 2008 Ding et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Ding, Yu
Xi, Ying
Chen, Ting
Wang, Ji-yong
Tao, Dong-lei
Wu, Zhi-Li
Li, Yi-ping
Li, Chen
Zeng, Rong
Li, Lin
Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation
title Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation
title_full Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation
title_fullStr Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation
title_full_unstemmed Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation
title_short Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation
title_sort caprin-2 enhances canonical wnt signaling through regulating lrp5/6 phosphorylation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528581/
https://www.ncbi.nlm.nih.gov/pubmed/18762581
http://dx.doi.org/10.1083/jcb.200803147
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