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MYPT1 O-GlcNAc modification regulates sphingosine-1-phosphate mediated contraction
Many intracellular proteins are modified by N-acetylglucosamine, a posttranslational modification termed O-GlcNAc. This modification is found on serine and threonine side-chains and has the potential to regulate signaling pathways through interplay with phosphorylation. Here, we discover and charact...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855082/ https://www.ncbi.nlm.nih.gov/pubmed/32929277 http://dx.doi.org/10.1038/s41589-020-0640-8 |
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author | Pedowitz, Nichole J. Batt, Anna R. Darabedian, Narek Pratt, Matthew R. |
author_facet | Pedowitz, Nichole J. Batt, Anna R. Darabedian, Narek Pratt, Matthew R. |
author_sort | Pedowitz, Nichole J. |
collection | PubMed |
description | Many intracellular proteins are modified by N-acetylglucosamine, a posttranslational modification termed O-GlcNAc. This modification is found on serine and threonine side-chains and has the potential to regulate signaling pathways through interplay with phosphorylation. Here, we discover and characterize one such example. We find that O-GlcNAc levels control the sensitivity of fibroblasts to actin contraction induced by the signaling lipid sphingosine-1-phosphate (S1P), culminating in the phosphorylation of myosin light chain (MLC) and cellular contraction. Specifically, O-GlcNAc modification of the phosphatase subunit MYPT1 inhibits this pathway by blocking MYPT1 phosphorylation, maintaining its activity and causing the dephosphorylation of MLC. Finally, we demonstrate that O-GlcNAc levels alter the sensitivity of primary human dermal fibroblasts in a collagen-matrix model of wound healing. Our findings have important implications for the role of O-GlcNAc in fibroblast motility and differentiation, particularly in diabetic wound healing. |
format | Online Article Text |
id | pubmed-7855082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-78550822021-03-14 MYPT1 O-GlcNAc modification regulates sphingosine-1-phosphate mediated contraction Pedowitz, Nichole J. Batt, Anna R. Darabedian, Narek Pratt, Matthew R. Nat Chem Biol Article Many intracellular proteins are modified by N-acetylglucosamine, a posttranslational modification termed O-GlcNAc. This modification is found on serine and threonine side-chains and has the potential to regulate signaling pathways through interplay with phosphorylation. Here, we discover and characterize one such example. We find that O-GlcNAc levels control the sensitivity of fibroblasts to actin contraction induced by the signaling lipid sphingosine-1-phosphate (S1P), culminating in the phosphorylation of myosin light chain (MLC) and cellular contraction. Specifically, O-GlcNAc modification of the phosphatase subunit MYPT1 inhibits this pathway by blocking MYPT1 phosphorylation, maintaining its activity and causing the dephosphorylation of MLC. Finally, we demonstrate that O-GlcNAc levels alter the sensitivity of primary human dermal fibroblasts in a collagen-matrix model of wound healing. Our findings have important implications for the role of O-GlcNAc in fibroblast motility and differentiation, particularly in diabetic wound healing. 2020-09-14 2021-02 /pmc/articles/PMC7855082/ /pubmed/32929277 http://dx.doi.org/10.1038/s41589-020-0640-8 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Pedowitz, Nichole J. Batt, Anna R. Darabedian, Narek Pratt, Matthew R. MYPT1 O-GlcNAc modification regulates sphingosine-1-phosphate mediated contraction |
title | MYPT1 O-GlcNAc modification regulates sphingosine-1-phosphate mediated contraction |
title_full | MYPT1 O-GlcNAc modification regulates sphingosine-1-phosphate mediated contraction |
title_fullStr | MYPT1 O-GlcNAc modification regulates sphingosine-1-phosphate mediated contraction |
title_full_unstemmed | MYPT1 O-GlcNAc modification regulates sphingosine-1-phosphate mediated contraction |
title_short | MYPT1 O-GlcNAc modification regulates sphingosine-1-phosphate mediated contraction |
title_sort | mypt1 o-glcnac modification regulates sphingosine-1-phosphate mediated contraction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855082/ https://www.ncbi.nlm.nih.gov/pubmed/32929277 http://dx.doi.org/10.1038/s41589-020-0640-8 |
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