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Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
Proteomics studies have revealed that SUMOylation is a widely used post-translational modification (PTM) in eukaryotes. However, how SUMO E1/2/3 complexes use different SUMO isoforms and recognize substrates remains largely unknown. Using a human proteome microarray-based activity screen, we identif...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Biochemistry and Molecular Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930406/ https://www.ncbi.nlm.nih.gov/pubmed/29438996 http://dx.doi.org/10.1074/mcp.RA117.000014 |
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author | Uzoma, Ijeoma Hu, Jianfei Cox, Eric Xia, Shuli Zhou, Jianying Rho, Hee-Sool Guzzo, Catherine Paul, Corry Ajala, Olutobi Goodwin, C. Rory Jeong, Junseop Moore, Cedric Zhang, Hui Meluh, Pamela Blackshaw, Seth Matunis, Michael Qian, Jiang Zhu, Heng |
author_facet | Uzoma, Ijeoma Hu, Jianfei Cox, Eric Xia, Shuli Zhou, Jianying Rho, Hee-Sool Guzzo, Catherine Paul, Corry Ajala, Olutobi Goodwin, C. Rory Jeong, Junseop Moore, Cedric Zhang, Hui Meluh, Pamela Blackshaw, Seth Matunis, Michael Qian, Jiang Zhu, Heng |
author_sort | Uzoma, Ijeoma |
collection | PubMed |
description | Proteomics studies have revealed that SUMOylation is a widely used post-translational modification (PTM) in eukaryotes. However, how SUMO E1/2/3 complexes use different SUMO isoforms and recognize substrates remains largely unknown. Using a human proteome microarray-based activity screen, we identified over 2500 proteins that undergo SUMO E3-dependent SUMOylation. We next constructed a SUMO isoform- and E3 ligase-dependent enzyme-substrate relationship network. Protein kinases were significantly enriched among SUMOylation substrates, suggesting crosstalk between phosphorylation and SUMOylation. Cell-based analyses of tyrosine kinase, PYK2, revealed that SUMOylation at four lysine residues promoted PYK2 autophosphorylation at tyrosine 402, which in turn enhanced its interaction with SRC and full activation of the SRC-PYK2 complex. SUMOylation on WT but not the 4KR mutant of PYK2 further elevated phosphorylation of the downstream components in the focal adhesion pathway, such as paxillin and Erk1/2, leading to significantly enhanced cell migration during wound healing. These studies illustrate how our SUMO E3 ligase-substrate network can be used to explore crosstalk between SUMOylation and other PTMs in many biological processes. |
format | Online Article Text |
id | pubmed-5930406 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-59304062018-05-03 Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration Uzoma, Ijeoma Hu, Jianfei Cox, Eric Xia, Shuli Zhou, Jianying Rho, Hee-Sool Guzzo, Catherine Paul, Corry Ajala, Olutobi Goodwin, C. Rory Jeong, Junseop Moore, Cedric Zhang, Hui Meluh, Pamela Blackshaw, Seth Matunis, Michael Qian, Jiang Zhu, Heng Mol Cell Proteomics Research Proteomics studies have revealed that SUMOylation is a widely used post-translational modification (PTM) in eukaryotes. However, how SUMO E1/2/3 complexes use different SUMO isoforms and recognize substrates remains largely unknown. Using a human proteome microarray-based activity screen, we identified over 2500 proteins that undergo SUMO E3-dependent SUMOylation. We next constructed a SUMO isoform- and E3 ligase-dependent enzyme-substrate relationship network. Protein kinases were significantly enriched among SUMOylation substrates, suggesting crosstalk between phosphorylation and SUMOylation. Cell-based analyses of tyrosine kinase, PYK2, revealed that SUMOylation at four lysine residues promoted PYK2 autophosphorylation at tyrosine 402, which in turn enhanced its interaction with SRC and full activation of the SRC-PYK2 complex. SUMOylation on WT but not the 4KR mutant of PYK2 further elevated phosphorylation of the downstream components in the focal adhesion pathway, such as paxillin and Erk1/2, leading to significantly enhanced cell migration during wound healing. These studies illustrate how our SUMO E3 ligase-substrate network can be used to explore crosstalk between SUMOylation and other PTMs in many biological processes. The American Society for Biochemistry and Molecular Biology 2018-05 2018-02-08 /pmc/articles/PMC5930406/ /pubmed/29438996 http://dx.doi.org/10.1074/mcp.RA117.000014 Text en © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) . |
spellingShingle | Research Uzoma, Ijeoma Hu, Jianfei Cox, Eric Xia, Shuli Zhou, Jianying Rho, Hee-Sool Guzzo, Catherine Paul, Corry Ajala, Olutobi Goodwin, C. Rory Jeong, Junseop Moore, Cedric Zhang, Hui Meluh, Pamela Blackshaw, Seth Matunis, Michael Qian, Jiang Zhu, Heng Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration |
title | Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
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title_full | Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
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title_fullStr | Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
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title_full_unstemmed | Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
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title_short | Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
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title_sort | global identification of small ubiquitin-related modifier (sumo) substrates reveals crosstalk between sumoylation and phosphorylation promotes cell migration |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930406/ https://www.ncbi.nlm.nih.gov/pubmed/29438996 http://dx.doi.org/10.1074/mcp.RA117.000014 |
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