A conserved non-canonical docking mechanism regulates the binding of dual specificity phosphatases to cell integrity mitogen-activated protein kinases (MAPKs) in budding and fission yeasts.
Dual-specificity MAPK phosphatases (MKPs) are essential for the negative regulation of MAPK pathways. Similar to other MAPK-interacting proteins, most MKPs bind MAPKs through specific docking domains known as D-motifs. However, we found that the Saccharomyces cerevisiae MKP Msg5 binds the MAPK Slt2...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3898958?pdf=render |
| _version_ | 1819231329283211264 |
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| author | Almudena Sacristán-Reviriego Marisa Madrid José Cansado Humberto Martín María Molina |
| author_facet | Almudena Sacristán-Reviriego Marisa Madrid José Cansado Humberto Martín María Molina |
| author_sort | Almudena Sacristán-Reviriego |
| collection | DOAJ |
| description | Dual-specificity MAPK phosphatases (MKPs) are essential for the negative regulation of MAPK pathways. Similar to other MAPK-interacting proteins, most MKPs bind MAPKs through specific docking domains known as D-motifs. However, we found that the Saccharomyces cerevisiae MKP Msg5 binds the MAPK Slt2 within the cell wall integrity (CWI) pathway through a distinct motif (IYT). Here, we demonstrate that the IYT motif mediates binding of the Msg5 paralogue Sdp1 to Slt2 as well as of the MKP Pmp1 to its CWI MAPK counterpart Pmk1 in the evolutionarily distant yeast Schizosaccharomyces pombe. As a consequence, removal of the IYT site in Msg5, Sdp1 and Pmp1 reduces MAPK trapping caused by the overexpression of catalytically inactive versions of these phosphatases. Accordingly, an intact IYT site is necessary for inactive Sdp1 to prevent nuclear accumulation of Slt2. We also show that both Ile and Tyr but not Thr are essential for the functionality of the IYT motif. These results provide mechanistic insight into MKP-MAPK interplay and stress the relevance of this conserved non-canonical docking site in the regulation of the CWI pathway in fungi. |
| first_indexed | 2024-12-23T11:43:14Z |
| format | Article |
| id | doaj.art-9a10d03d8e504598aed5292f61ae367d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T11:43:14Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9a10d03d8e504598aed5292f61ae367d2022-12-21T17:48:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8539010.1371/journal.pone.0085390A conserved non-canonical docking mechanism regulates the binding of dual specificity phosphatases to cell integrity mitogen-activated protein kinases (MAPKs) in budding and fission yeasts.Almudena Sacristán-ReviriegoMarisa MadridJosé CansadoHumberto MartínMaría MolinaDual-specificity MAPK phosphatases (MKPs) are essential for the negative regulation of MAPK pathways. Similar to other MAPK-interacting proteins, most MKPs bind MAPKs through specific docking domains known as D-motifs. However, we found that the Saccharomyces cerevisiae MKP Msg5 binds the MAPK Slt2 within the cell wall integrity (CWI) pathway through a distinct motif (IYT). Here, we demonstrate that the IYT motif mediates binding of the Msg5 paralogue Sdp1 to Slt2 as well as of the MKP Pmp1 to its CWI MAPK counterpart Pmk1 in the evolutionarily distant yeast Schizosaccharomyces pombe. As a consequence, removal of the IYT site in Msg5, Sdp1 and Pmp1 reduces MAPK trapping caused by the overexpression of catalytically inactive versions of these phosphatases. Accordingly, an intact IYT site is necessary for inactive Sdp1 to prevent nuclear accumulation of Slt2. We also show that both Ile and Tyr but not Thr are essential for the functionality of the IYT motif. These results provide mechanistic insight into MKP-MAPK interplay and stress the relevance of this conserved non-canonical docking site in the regulation of the CWI pathway in fungi.http://europepmc.org/articles/PMC3898958?pdf=render |
| spellingShingle | Almudena Sacristán-Reviriego Marisa Madrid José Cansado Humberto Martín María Molina A conserved non-canonical docking mechanism regulates the binding of dual specificity phosphatases to cell integrity mitogen-activated protein kinases (MAPKs) in budding and fission yeasts. PLoS ONE |
| title | A conserved non-canonical docking mechanism regulates the binding of dual specificity phosphatases to cell integrity mitogen-activated protein kinases (MAPKs) in budding and fission yeasts. |
| title_full | A conserved non-canonical docking mechanism regulates the binding of dual specificity phosphatases to cell integrity mitogen-activated protein kinases (MAPKs) in budding and fission yeasts. |
| title_fullStr | A conserved non-canonical docking mechanism regulates the binding of dual specificity phosphatases to cell integrity mitogen-activated protein kinases (MAPKs) in budding and fission yeasts. |
| title_full_unstemmed | A conserved non-canonical docking mechanism regulates the binding of dual specificity phosphatases to cell integrity mitogen-activated protein kinases (MAPKs) in budding and fission yeasts. |
| title_short | A conserved non-canonical docking mechanism regulates the binding of dual specificity phosphatases to cell integrity mitogen-activated protein kinases (MAPKs) in budding and fission yeasts. |
| title_sort | conserved non canonical docking mechanism regulates the binding of dual specificity phosphatases to cell integrity mitogen activated protein kinases mapks in budding and fission yeasts |
| url | http://europepmc.org/articles/PMC3898958?pdf=render |
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