Different modulation of the outputs of yeast MAPK-mediated pathways by distinct stimuli and isoforms of the dual-specificity phosphatase Msg5.
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.
Marín
María José
MJ
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Pza Ramón y Cajal s/n, 28040, Madrid, Spain.
Flández
Marta
M
Bermejo
Clara
C
Arroyo
Javier
J
Martín
Humberto
H
Molina
María
M
D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005800:Genes, Fungal; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D007527:Isoenzymes; C489601:RIM101 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C075580:FUS3 protein, S cerevisiae; C541984:KSS1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae; D054637:Dual-Specificity Phosphatases; C085791:MSG5 protein, S cerevisiae; D017027:Protein Tyrosine Phosphatases