Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1782158886203031552 |
---|---|
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. |
format | Text |
id | pubmed-2528581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT dingyu caprin2enhancescanonicalwntsignalingthroughregulatinglrp56phosphorylation AT xiying caprin2enhancescanonicalwntsignalingthroughregulatinglrp56phosphorylation AT chenting caprin2enhancescanonicalwntsignalingthroughregulatinglrp56phosphorylation AT wangjiyong caprin2enhancescanonicalwntsignalingthroughregulatinglrp56phosphorylation AT taodonglei caprin2enhancescanonicalwntsignalingthroughregulatinglrp56phosphorylation AT wuzhili caprin2enhancescanonicalwntsignalingthroughregulatinglrp56phosphorylation AT liyiping caprin2enhancescanonicalwntsignalingthroughregulatinglrp56phosphorylation AT lichen caprin2enhancescanonicalwntsignalingthroughregulatinglrp56phosphorylation AT zengrong caprin2enhancescanonicalwntsignalingthroughregulatinglrp56phosphorylation AT lilin caprin2enhancescanonicalwntsignalingthroughregulatinglrp56phosphorylation |