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E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion
E-cadherin is highly phosphorylated within its β-catenin–binding region, and this phosphorylation increases its affinity for β-catenin in vitro. However, the identification of key serines responsible for most cadherin phosphorylation and the adhesive consequences of modification at such serines have...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142610/ https://www.ncbi.nlm.nih.gov/pubmed/24966173 http://dx.doi.org/10.1091/mbc.E14-01-0690 |
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author | McEwen, Abbye E. Maher, Meghan T. Mo, Rigen Gottardi, Cara J. |
author_facet | McEwen, Abbye E. Maher, Meghan T. Mo, Rigen Gottardi, Cara J. |
author_sort | McEwen, Abbye E. |
collection | PubMed |
description | E-cadherin is highly phosphorylated within its β-catenin–binding region, and this phosphorylation increases its affinity for β-catenin in vitro. However, the identification of key serines responsible for most cadherin phosphorylation and the adhesive consequences of modification at such serines have remained unknown. In this study, we show that as few as three serines in the β-catenin–binding domain of E-cadherin are responsible for most radioactive phosphate incorporation. These serines are required for binding to β-catenin and the mutual stability of both E-cadherin and β-catenin. Cells expressing a phosphodeficient (3S>A) E-cadherin exhibit minimal cell–cell adhesion due to enhanced endocytosis and degradation through a lysosomal compartment. Conversely, negative charge substitution at these serines (3S>D) antagonizes cadherin endocytosis and restores wild-type levels of adhesion. The cadherin kinase is membrane proximal and modifies the cadherin before it reaches the cell surface. Together these data suggest that E-cadherin phosphorylation is largely constitutive and integral to cadherin–catenin complex formation, surface stability, and function. |
format | Online Article Text |
id | pubmed-4142610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-41426102014-10-30 E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion McEwen, Abbye E. Maher, Meghan T. Mo, Rigen Gottardi, Cara J. Mol Biol Cell Articles E-cadherin is highly phosphorylated within its β-catenin–binding region, and this phosphorylation increases its affinity for β-catenin in vitro. However, the identification of key serines responsible for most cadherin phosphorylation and the adhesive consequences of modification at such serines have remained unknown. In this study, we show that as few as three serines in the β-catenin–binding domain of E-cadherin are responsible for most radioactive phosphate incorporation. These serines are required for binding to β-catenin and the mutual stability of both E-cadherin and β-catenin. Cells expressing a phosphodeficient (3S>A) E-cadherin exhibit minimal cell–cell adhesion due to enhanced endocytosis and degradation through a lysosomal compartment. Conversely, negative charge substitution at these serines (3S>D) antagonizes cadherin endocytosis and restores wild-type levels of adhesion. The cadherin kinase is membrane proximal and modifies the cadherin before it reaches the cell surface. Together these data suggest that E-cadherin phosphorylation is largely constitutive and integral to cadherin–catenin complex formation, surface stability, and function. The American Society for Cell Biology 2014-08-15 /pmc/articles/PMC4142610/ /pubmed/24966173 http://dx.doi.org/10.1091/mbc.E14-01-0690 Text en © 2014 McEwen, Maher, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles McEwen, Abbye E. Maher, Meghan T. Mo, Rigen Gottardi, Cara J. E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion |
title | E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion |
title_full | E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion |
title_fullStr | E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion |
title_full_unstemmed | E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion |
title_short | E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion |
title_sort | e-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142610/ https://www.ncbi.nlm.nih.gov/pubmed/24966173 http://dx.doi.org/10.1091/mbc.E14-01-0690 |
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