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Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases
Protein tyrosine phosphatases dephosphorylate tyrosine residues of proteins, whereas, dual specificity phosphatases (DUSPs) are a subgroup of protein tyrosine phosphatases that dephosphorylate not only Tyr(P) residue, but also the Ser(P) and Thr(P) residues of proteins. The DUSPs are linked to the r...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547750/ https://www.ncbi.nlm.nih.gov/pubmed/26302245 http://dx.doi.org/10.1371/journal.pone.0134984 |
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author | Zhao, Bryan M. Keasey, Sarah L. Tropea, Joseph E. Lountos, George T. Dyas, Beverly K. Cherry, Scott Raran-Kurussi, Sreejith Waugh, David S. Ulrich, Robert G. |
author_facet | Zhao, Bryan M. Keasey, Sarah L. Tropea, Joseph E. Lountos, George T. Dyas, Beverly K. Cherry, Scott Raran-Kurussi, Sreejith Waugh, David S. Ulrich, Robert G. |
author_sort | Zhao, Bryan M. |
collection | PubMed |
description | Protein tyrosine phosphatases dephosphorylate tyrosine residues of proteins, whereas, dual specificity phosphatases (DUSPs) are a subgroup of protein tyrosine phosphatases that dephosphorylate not only Tyr(P) residue, but also the Ser(P) and Thr(P) residues of proteins. The DUSPs are linked to the regulation of many cellular functions and signaling pathways. Though many cellular targets of DUSPs are known, the relationship between catalytic activity and substrate specificity is poorly defined. We investigated the interactions of peptide substrates with select DUSPs of four types: MAP kinases (DUSP1 and DUSP7), atypical (DUSP3, DUSP14, DUSP22 and DUSP27), viral (variola VH1), and Cdc25 (A-C). Phosphatase recognition sites were experimentally determined by measuring dephosphorylation of 6,218 microarrayed Tyr(P) peptides representing confirmed and theoretical phosphorylation motifs from the cellular proteome. A broad continuum of dephosphorylation was observed across the microarrayed peptide substrates for all phosphatases, suggesting a complex relationship between substrate sequence recognition and optimal activity. Further analysis of peptide dephosphorylation by hierarchical clustering indicated that DUSPs could be organized by substrate sequence motifs, and peptide-specificities by phylogenetic relationships among the catalytic domains. The most highly dephosphorylated peptides represented proteins from 29 cell-signaling pathways, greatly expanding the list of potential targets of DUSPs. These newly identified DUSP substrates will be important for examining structure-activity relationships with physiologically relevant targets. |
format | Online Article Text |
id | pubmed-4547750 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45477502015-09-01 Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases Zhao, Bryan M. Keasey, Sarah L. Tropea, Joseph E. Lountos, George T. Dyas, Beverly K. Cherry, Scott Raran-Kurussi, Sreejith Waugh, David S. Ulrich, Robert G. PLoS One Research Article Protein tyrosine phosphatases dephosphorylate tyrosine residues of proteins, whereas, dual specificity phosphatases (DUSPs) are a subgroup of protein tyrosine phosphatases that dephosphorylate not only Tyr(P) residue, but also the Ser(P) and Thr(P) residues of proteins. The DUSPs are linked to the regulation of many cellular functions and signaling pathways. Though many cellular targets of DUSPs are known, the relationship between catalytic activity and substrate specificity is poorly defined. We investigated the interactions of peptide substrates with select DUSPs of four types: MAP kinases (DUSP1 and DUSP7), atypical (DUSP3, DUSP14, DUSP22 and DUSP27), viral (variola VH1), and Cdc25 (A-C). Phosphatase recognition sites were experimentally determined by measuring dephosphorylation of 6,218 microarrayed Tyr(P) peptides representing confirmed and theoretical phosphorylation motifs from the cellular proteome. A broad continuum of dephosphorylation was observed across the microarrayed peptide substrates for all phosphatases, suggesting a complex relationship between substrate sequence recognition and optimal activity. Further analysis of peptide dephosphorylation by hierarchical clustering indicated that DUSPs could be organized by substrate sequence motifs, and peptide-specificities by phylogenetic relationships among the catalytic domains. The most highly dephosphorylated peptides represented proteins from 29 cell-signaling pathways, greatly expanding the list of potential targets of DUSPs. These newly identified DUSP substrates will be important for examining structure-activity relationships with physiologically relevant targets. Public Library of Science 2015-08-24 /pmc/articles/PMC4547750/ /pubmed/26302245 http://dx.doi.org/10.1371/journal.pone.0134984 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Zhao, Bryan M. Keasey, Sarah L. Tropea, Joseph E. Lountos, George T. Dyas, Beverly K. Cherry, Scott Raran-Kurussi, Sreejith Waugh, David S. Ulrich, Robert G. Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases |
title | Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases |
title_full | Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases |
title_fullStr | Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases |
title_full_unstemmed | Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases |
title_short | Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases |
title_sort | phosphotyrosine substrate sequence motifs for dual specificity phosphatases |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547750/ https://www.ncbi.nlm.nih.gov/pubmed/26302245 http://dx.doi.org/10.1371/journal.pone.0134984 |
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