The activity of protein phosphatases on mitogen-activated protein kinases (MAPKS) is essential in the modulation of the final outcome of MAPK-signalling pathways. The yeast dual-specificity phosphatase (DSP) Msg5, expressed as two isoforms of different length, dephosphorylates the MAPKs of mating and cell integrity pathways, Fus3 and Slt2, respectively, but its action on the MAPK Kss1 is unclear. Here we analyse the global impact of Msg5 on the yeast transcriptome. Both Fus3- and Slt2- but not Kss1-mediated gene expression is induced in cells lacking Msg5. However, although these cells show high Slt2 phosphorylation, the Rlm1-dependent Slt2-regulated transcriptional response is weak. Therefore, mechanisms concomitant with Slt2 phosphorylation are required for a strong Rlm1 activation. The limited Slt2 activity on Rlm1 is not a specific effect on this substrate but a consequence of its low kinase activity in msg5Delta cells. Lack of Msg5 does not increase Kss1 phosphorylation although both proteins physically interact. Both Msg5 isoforms interact similarly with Slt2, whereas the long form binds Fus3 with higher affinity and consequently down-regulates it more efficiently than the short one. We propose that specific binding of DSP isoforms to distinct MAPKs provides a novel mechanism for fine tuning different pathways by the same phosphatase.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|