RT Journal Article
T1 Distinct Docking Mechanisms Mediate Interactions between the Msg5 Phosphatase and Mating or Cell Integrity Mitogen-activated Protein Kinases (MAPKs) in Saccharomyces cerevisiae
A1 Palacios, Lorena
A1 Dickinson, Robin J.
A1 Sacristán Reviriego, Almudena
A1 Didmon, Mark P.
A1 Marín Cuenda, María José
A1 Martín Brieva, Humberto
A1 Keyse, Stephen M.
A1 Molina Martín, María
AB MAPK phosphatases (MKPs) are negative regulators of signaling pathways with distinct MAPK substrate specificities. For example, the yeast dual specificity phosphatase Msg5 dephosphorylates the Fus3 and Slt2 MAPKs operating in the mating and cell wall integrity pathways, respectively. Like other MAPKinteracting proteins, most MKPs bind MAPKs through specific docking domains. These include D-motifs, which contain basicresidues that interact with acidic residues in the common docking (CD) domain of MAPKs. Here we show that Msg5 interacts not only with Fus3, Kss1, and Slt2 but also with the pseudokinase Slt2 paralog Mlp1. Using yeast two-hybrid and in vitro interaction assays, we have identified distinct regions within the N-terminal domain of Msg5 that differentially bind either the MAPKs Fus3 and Kss1 or Slt2 and Mlp1. Whereas a canonical D-site within Msg5 mediates interaction with the CD domains of Fus3 and Kss1, a novel motif (102IYT104) within Msg5 isinvolved in binding to Slt2 and Mlp1. Furthermore, mutation of this site prevents the phosphorylation of Msg5 by Slt2. This motif is conserved in Sdp1, another MKP that dephosphorylates Slt2, as well as in Msg5 orthologs from other yeast species. A region spanning amino acids 274–373 within Slt2 and Mlp1 mediates binding to this Msg5 motif in a CD domain-independent manner. In contrast, Slt2 uses its CD domain to bind to itsupstream activator Mkk1. This binding flexibility may allow MAPK pathways to exploit additional regulatory controls in order to provide fine modulation of both pathway activity and specificity.
PB Elsevier BV
SN 0021-9258
YR 2011
FD 2011-12
LK https://hdl.handle.net/20.500.14352/114179
UL https://hdl.handle.net/20.500.14352/114179
LA eng
NO Ministerio de Ciencia e Innovación (España)
NO Cancer Research UK Program
DS Docta Complutense
RD 11 abr 2025