RT Journal Article
T1 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.
A1 Sacristán Reviriego, Almudena
A1 Madrid, Marisa
A1 Cansado, José
A1 Martín, Humberto
A1 Molina, María
AB 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.
PB Public Library of Science
SN 1932-6203
YR 2014
FD 2014-01-22
LK https://hdl.handle.net/20.500.14352/34925
UL https://hdl.handle.net/20.500.14352/34925
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)
NO Comunidad de Madrid
NO Ministerio de Ciencia e Innovación (MICINN)
NO Fundación Séneca
NO European Regional Development Fund (ERDF)
DS Docta Complutense
RD 8 abr 2025