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The homophilic receptor PTPRK selectively dephosphorylates multiple junctional regulators to promote cell–cell adhesion
Cell-cell communication in multicellular organisms depends on the dynamic and reversible phosphorylation of protein tyrosine residues. The receptor-linked protein tyrosine phosphatases (RPTPs) receive cues from the extracellular environment and are well placed to influence cell signaling. However, t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440744/ https://www.ncbi.nlm.nih.gov/pubmed/30924770 http://dx.doi.org/10.7554/eLife.44597 |
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author | Fearnley, Gareth W Young, Katherine A Edgar, James R Antrobus, Robin Hay, Iain M Liang, Wei-Ching Martinez-Martin, Nadia Lin, WeiYu Deane, Janet E Sharpe, Hayley J |
author_facet | Fearnley, Gareth W Young, Katherine A Edgar, James R Antrobus, Robin Hay, Iain M Liang, Wei-Ching Martinez-Martin, Nadia Lin, WeiYu Deane, Janet E Sharpe, Hayley J |
author_sort | Fearnley, Gareth W |
collection | PubMed |
description | Cell-cell communication in multicellular organisms depends on the dynamic and reversible phosphorylation of protein tyrosine residues. The receptor-linked protein tyrosine phosphatases (RPTPs) receive cues from the extracellular environment and are well placed to influence cell signaling. However, the direct events downstream of these receptors have been challenging to resolve. We report here that the homophilic receptor PTPRK is stabilized at cell-cell contacts in epithelial cells. By combining interaction studies, quantitative tyrosine phosphoproteomics, proximity labeling and dephosphorylation assays we identify high confidence PTPRK substrates. PTPRK directly and selectively dephosphorylates at least five substrates, including Afadin, PARD3 and δ-catenin family members, which are all important cell-cell adhesion regulators. In line with this, loss of PTPRK phosphatase activity leads to disrupted cell junctions and increased invasive characteristics. Thus, identifying PTPRK substrates provides insight into its downstream signaling and a potential molecular explanation for its proposed tumor suppressor function. |
format | Online Article Text |
id | pubmed-6440744 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-64407442019-04-01 The homophilic receptor PTPRK selectively dephosphorylates multiple junctional regulators to promote cell–cell adhesion Fearnley, Gareth W Young, Katherine A Edgar, James R Antrobus, Robin Hay, Iain M Liang, Wei-Ching Martinez-Martin, Nadia Lin, WeiYu Deane, Janet E Sharpe, Hayley J eLife Cell Biology Cell-cell communication in multicellular organisms depends on the dynamic and reversible phosphorylation of protein tyrosine residues. The receptor-linked protein tyrosine phosphatases (RPTPs) receive cues from the extracellular environment and are well placed to influence cell signaling. However, the direct events downstream of these receptors have been challenging to resolve. We report here that the homophilic receptor PTPRK is stabilized at cell-cell contacts in epithelial cells. By combining interaction studies, quantitative tyrosine phosphoproteomics, proximity labeling and dephosphorylation assays we identify high confidence PTPRK substrates. PTPRK directly and selectively dephosphorylates at least five substrates, including Afadin, PARD3 and δ-catenin family members, which are all important cell-cell adhesion regulators. In line with this, loss of PTPRK phosphatase activity leads to disrupted cell junctions and increased invasive characteristics. Thus, identifying PTPRK substrates provides insight into its downstream signaling and a potential molecular explanation for its proposed tumor suppressor function. eLife Sciences Publications, Ltd 2019-03-29 /pmc/articles/PMC6440744/ /pubmed/30924770 http://dx.doi.org/10.7554/eLife.44597 Text en © 2019, Fearnley et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Fearnley, Gareth W Young, Katherine A Edgar, James R Antrobus, Robin Hay, Iain M Liang, Wei-Ching Martinez-Martin, Nadia Lin, WeiYu Deane, Janet E Sharpe, Hayley J The homophilic receptor PTPRK selectively dephosphorylates multiple junctional regulators to promote cell–cell adhesion |
title | The homophilic receptor PTPRK selectively dephosphorylates multiple junctional regulators to promote cell–cell adhesion |
title_full | The homophilic receptor PTPRK selectively dephosphorylates multiple junctional regulators to promote cell–cell adhesion |
title_fullStr | The homophilic receptor PTPRK selectively dephosphorylates multiple junctional regulators to promote cell–cell adhesion |
title_full_unstemmed | The homophilic receptor PTPRK selectively dephosphorylates multiple junctional regulators to promote cell–cell adhesion |
title_short | The homophilic receptor PTPRK selectively dephosphorylates multiple junctional regulators to promote cell–cell adhesion |
title_sort | homophilic receptor ptprk selectively dephosphorylates multiple junctional regulators to promote cell–cell adhesion |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440744/ https://www.ncbi.nlm.nih.gov/pubmed/30924770 http://dx.doi.org/10.7554/eLife.44597 |
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