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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
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.
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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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