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Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis
Ran is an essential GTPase that controls nucleocytoplasmic transport, mitosis, and nuclear envelope formation. These functions are regulated by interaction of Ran with different partners, and by formation of a Ran-GTP gradient emanating from chromatin. Here, we identify a novel level of Ran regulati...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935564/ https://www.ncbi.nlm.nih.gov/pubmed/20805321 http://dx.doi.org/10.1083/jcb.200912056 |
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author | Bompard, Guillaume Rabeharivelo, Gabriel Frank, Marie Cau, Julien Delsert, Claude Morin, Nathalie |
author_facet | Bompard, Guillaume Rabeharivelo, Gabriel Frank, Marie Cau, Julien Delsert, Claude Morin, Nathalie |
author_sort | Bompard, Guillaume |
collection | PubMed |
description | Ran is an essential GTPase that controls nucleocytoplasmic transport, mitosis, and nuclear envelope formation. These functions are regulated by interaction of Ran with different partners, and by formation of a Ran-GTP gradient emanating from chromatin. Here, we identify a novel level of Ran regulation. We show that Ran is a substrate for p21-activated kinase 4 (PAK4) and that its phosphorylation on serine-135 increases during mitosis. The endogenous phosphorylated Ran and active PAK4 dynamically associate with different components of the microtubule spindle during mitotic progression. A GDP-bound Ran phosphomimetic mutant cannot undergo RCC1-mediated GDP/GTP exchange and cannot induce microtubule asters in mitotic Xenopus egg extracts. Conversely, phosphorylation of GTP-bound Ran facilitates aster nucleation. Finally, phosphorylation of Ran on serine-135 impedes its binding to RCC1 and RanGAP1. Our study suggests that PAK4-mediated phosphorylation of GDP- or GTP-bound Ran regulates the assembly of Ran-dependent complexes on the mitotic spindle. |
format | Text |
id | pubmed-2935564 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-29355642011-03-06 Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis Bompard, Guillaume Rabeharivelo, Gabriel Frank, Marie Cau, Julien Delsert, Claude Morin, Nathalie J Cell Biol Research Articles Ran is an essential GTPase that controls nucleocytoplasmic transport, mitosis, and nuclear envelope formation. These functions are regulated by interaction of Ran with different partners, and by formation of a Ran-GTP gradient emanating from chromatin. Here, we identify a novel level of Ran regulation. We show that Ran is a substrate for p21-activated kinase 4 (PAK4) and that its phosphorylation on serine-135 increases during mitosis. The endogenous phosphorylated Ran and active PAK4 dynamically associate with different components of the microtubule spindle during mitotic progression. A GDP-bound Ran phosphomimetic mutant cannot undergo RCC1-mediated GDP/GTP exchange and cannot induce microtubule asters in mitotic Xenopus egg extracts. Conversely, phosphorylation of GTP-bound Ran facilitates aster nucleation. Finally, phosphorylation of Ran on serine-135 impedes its binding to RCC1 and RanGAP1. Our study suggests that PAK4-mediated phosphorylation of GDP- or GTP-bound Ran regulates the assembly of Ran-dependent complexes on the mitotic spindle. The Rockefeller University Press 2010-09-06 /pmc/articles/PMC2935564/ /pubmed/20805321 http://dx.doi.org/10.1083/jcb.200912056 Text en © 2010 Bompard et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Bompard, Guillaume Rabeharivelo, Gabriel Frank, Marie Cau, Julien Delsert, Claude Morin, Nathalie Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis |
title | Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis |
title_full | Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis |
title_fullStr | Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis |
title_full_unstemmed | Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis |
title_short | Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis |
title_sort | subgroup ii pak-mediated phosphorylation regulates ran activity during mitosis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935564/ https://www.ncbi.nlm.nih.gov/pubmed/20805321 http://dx.doi.org/10.1083/jcb.200912056 |
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