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Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function
The mitogen-activated protein kinase-activated protein kinase-5 (MK5) resides predominantly in the nucleus of resting cells, but p38(MAPK), extracellular signal-regulated kinases-3 and -4 (ERK3 and ERK4), and protein kinase A (PKA) induce nucleocytoplasmic redistribution of MK5. The mechanism by whi...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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SP Birkhäuser Verlag Basel
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037495/ https://www.ncbi.nlm.nih.gov/pubmed/20734105 http://dx.doi.org/10.1007/s00018-010-0496-2 |
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author | Kostenko, Sergiy Shiryaev, Alexey Gerits, Nancy Dumitriu, Gianina Klenow, Helle Johannessen, Mona Moens, Ugo |
author_facet | Kostenko, Sergiy Shiryaev, Alexey Gerits, Nancy Dumitriu, Gianina Klenow, Helle Johannessen, Mona Moens, Ugo |
author_sort | Kostenko, Sergiy |
collection | PubMed |
description | The mitogen-activated protein kinase-activated protein kinase-5 (MK5) resides predominantly in the nucleus of resting cells, but p38(MAPK), extracellular signal-regulated kinases-3 and -4 (ERK3 and ERK4), and protein kinase A (PKA) induce nucleocytoplasmic redistribution of MK5. The mechanism by which PKA causes nuclear export remains unsolved. In the study reported here we demonstrated that Ser-115 is an in vitro PKA phosphoacceptor site, and that PKA, but not p38(MAPK), ERK3 or ERK4, is unable to redistribute MK5 S115A to the cytoplasm. However, the phosphomimicking MK5 S115D mutant resides in the cytoplasm in untreated cells. While p38(MAPK), ERK3 and ERK4 fail to trigger nuclear export of the kinase dead T182A and K51E MK5 mutants, S115D/T182A and K51E/S115D mutants were able to enter the cytoplasm of resting cells. Finally, we demonstrated that mutations in Ser-115 affect the biological properties of MK5. Taken together, our results suggest that Ser-115 plays an essential role in PKA-regulated nuclear export of MK5, and that it also may regulate the biological functions of MK5. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-010-0496-2) contains supplementary material, which is available to authorized users. |
format | Text |
id | pubmed-3037495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | SP Birkhäuser Verlag Basel |
record_format | MEDLINE/PubMed |
spelling | pubmed-30374952011-03-16 Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function Kostenko, Sergiy Shiryaev, Alexey Gerits, Nancy Dumitriu, Gianina Klenow, Helle Johannessen, Mona Moens, Ugo Cell Mol Life Sci Research Article The mitogen-activated protein kinase-activated protein kinase-5 (MK5) resides predominantly in the nucleus of resting cells, but p38(MAPK), extracellular signal-regulated kinases-3 and -4 (ERK3 and ERK4), and protein kinase A (PKA) induce nucleocytoplasmic redistribution of MK5. The mechanism by which PKA causes nuclear export remains unsolved. In the study reported here we demonstrated that Ser-115 is an in vitro PKA phosphoacceptor site, and that PKA, but not p38(MAPK), ERK3 or ERK4, is unable to redistribute MK5 S115A to the cytoplasm. However, the phosphomimicking MK5 S115D mutant resides in the cytoplasm in untreated cells. While p38(MAPK), ERK3 and ERK4 fail to trigger nuclear export of the kinase dead T182A and K51E MK5 mutants, S115D/T182A and K51E/S115D mutants were able to enter the cytoplasm of resting cells. Finally, we demonstrated that mutations in Ser-115 affect the biological properties of MK5. Taken together, our results suggest that Ser-115 plays an essential role in PKA-regulated nuclear export of MK5, and that it also may regulate the biological functions of MK5. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-010-0496-2) contains supplementary material, which is available to authorized users. SP Birkhäuser Verlag Basel 2010-08-25 2011 /pmc/articles/PMC3037495/ /pubmed/20734105 http://dx.doi.org/10.1007/s00018-010-0496-2 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Research Article Kostenko, Sergiy Shiryaev, Alexey Gerits, Nancy Dumitriu, Gianina Klenow, Helle Johannessen, Mona Moens, Ugo Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function |
title | Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function |
title_full | Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function |
title_fullStr | Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function |
title_full_unstemmed | Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function |
title_short | Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function |
title_sort | serine residue 115 of mapk-activated protein kinase mk5 is crucial for its pka-regulated nuclear export and biological function |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037495/ https://www.ncbi.nlm.nih.gov/pubmed/20734105 http://dx.doi.org/10.1007/s00018-010-0496-2 |
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