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LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression
In the mitotic exit network of budding yeast, Dbf2 kinase phosphorylates and regulates Cdc14 phosphatase. In contrast, no phosphatase substrates of LATS1/WARTS kinase, the mammalian equivalent of Dbf2, has been reported. To address this discrepancy, we performed phosphoproteomic screening using LATS...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404884/ https://www.ncbi.nlm.nih.gov/pubmed/22641346 http://dx.doi.org/10.1083/jcb.201110110 |
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author | Chiyoda, Tatsuyuki Sugiyama, Naoyuki Shimizu, Takatsune Naoe, Hideaki Kobayashi, Yusuke Ishizawa, Jo Arima, Yoshimi Tsuda, Hiroshi Ito, Masaaki Kaibuchi, Kozo Aoki, Daisuke Ishihama, Yasushi Saya, Hideyuki Kuninaka, Shinji |
author_facet | Chiyoda, Tatsuyuki Sugiyama, Naoyuki Shimizu, Takatsune Naoe, Hideaki Kobayashi, Yusuke Ishizawa, Jo Arima, Yoshimi Tsuda, Hiroshi Ito, Masaaki Kaibuchi, Kozo Aoki, Daisuke Ishihama, Yasushi Saya, Hideyuki Kuninaka, Shinji |
author_sort | Chiyoda, Tatsuyuki |
collection | PubMed |
description | In the mitotic exit network of budding yeast, Dbf2 kinase phosphorylates and regulates Cdc14 phosphatase. In contrast, no phosphatase substrates of LATS1/WARTS kinase, the mammalian equivalent of Dbf2, has been reported. To address this discrepancy, we performed phosphoproteomic screening using LATS1 kinase. Screening identified MYPT1 (myosin phosphatase–targeting subunit 1) as a new substrate for LATS1. LATS1 directly and preferentially phosphorylated serine 445 (S445) of MYPT1. An MYPT1 mutant (S445A) failed to dephosphorylate Thr 210 of PLK1 (pololike kinase 1), thereby activating PLK1. This suggests that LATS1 promotes MYPT1 to antagonize PLK1 activity. Consistent with this, LATS1-depleted HeLa cells or fibroblasts from LATS1 knockout mice showed increased PLK1 activity. We also found deoxyribonucleic acid (DNA) damage–induced LATS1 activation caused PLK1 suppression via the phosphorylation of MYPT1 S445. Furthermore, LATS1 knockdown cells showed reduced G2 checkpoint arrest after DNA damage. These results indicate that LATS1 phosphorylates a phosphatase as does the yeast Dbf2 and demonstrate a novel role of LATS1 in controlling PLK1 at the G2 DNA damage checkpoint. |
format | Online Article Text |
id | pubmed-3404884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34048842012-11-28 LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression Chiyoda, Tatsuyuki Sugiyama, Naoyuki Shimizu, Takatsune Naoe, Hideaki Kobayashi, Yusuke Ishizawa, Jo Arima, Yoshimi Tsuda, Hiroshi Ito, Masaaki Kaibuchi, Kozo Aoki, Daisuke Ishihama, Yasushi Saya, Hideyuki Kuninaka, Shinji J Cell Biol Research Articles In the mitotic exit network of budding yeast, Dbf2 kinase phosphorylates and regulates Cdc14 phosphatase. In contrast, no phosphatase substrates of LATS1/WARTS kinase, the mammalian equivalent of Dbf2, has been reported. To address this discrepancy, we performed phosphoproteomic screening using LATS1 kinase. Screening identified MYPT1 (myosin phosphatase–targeting subunit 1) as a new substrate for LATS1. LATS1 directly and preferentially phosphorylated serine 445 (S445) of MYPT1. An MYPT1 mutant (S445A) failed to dephosphorylate Thr 210 of PLK1 (pololike kinase 1), thereby activating PLK1. This suggests that LATS1 promotes MYPT1 to antagonize PLK1 activity. Consistent with this, LATS1-depleted HeLa cells or fibroblasts from LATS1 knockout mice showed increased PLK1 activity. We also found deoxyribonucleic acid (DNA) damage–induced LATS1 activation caused PLK1 suppression via the phosphorylation of MYPT1 S445. Furthermore, LATS1 knockdown cells showed reduced G2 checkpoint arrest after DNA damage. These results indicate that LATS1 phosphorylates a phosphatase as does the yeast Dbf2 and demonstrate a novel role of LATS1 in controlling PLK1 at the G2 DNA damage checkpoint. The Rockefeller University Press 2012-05-28 /pmc/articles/PMC3404884/ /pubmed/22641346 http://dx.doi.org/10.1083/jcb.201110110 Text en © 2012 Chiyoda 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 Chiyoda, Tatsuyuki Sugiyama, Naoyuki Shimizu, Takatsune Naoe, Hideaki Kobayashi, Yusuke Ishizawa, Jo Arima, Yoshimi Tsuda, Hiroshi Ito, Masaaki Kaibuchi, Kozo Aoki, Daisuke Ishihama, Yasushi Saya, Hideyuki Kuninaka, Shinji LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression |
title | LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression |
title_full | LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression |
title_fullStr | LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression |
title_full_unstemmed | LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression |
title_short | LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression |
title_sort | lats1/warts phosphorylates mypt1 to counteract plk1 and regulate mammalian mitotic progression |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404884/ https://www.ncbi.nlm.nih.gov/pubmed/22641346 http://dx.doi.org/10.1083/jcb.201110110 |
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