title: Differential input by Ste5 scaffold and Msg5 phosphatase route a MAPK cascade to multiple outcomes.
abstract: Pathway specificity is poorly understood for mitogen-activated protein kinase (MAPK) cascades that control different outputs in response to different stimuli. In yeast, it is not known how the same MAPK cascade activates Kss1 MAPK to promote invasive growth (IG) and proliferation, and both Fus3 and Kss1 MAPKs to promote mating. Previous work has suggested that the Kss1 MAPK cascade is activated independently of the mating G protein (Ste4)-scaffold (Ste5) system during IG. Here we demonstrate that Ste4 and Ste5 activate Kss1 during IG and in response to multiple stimuli including butanol. Ste5 activates Kss1 by generating a pool of active MAPKKK (Ste11), whereas additional scaffolding is needed to activate Fus3. Scaffold-independent activation of Kss1 can occur at multiple steps in the pathway, whereas Fus3 is strictly dependent on the scaffold. Pathway specificity is linked to Kss1 immunity to a MAPK phosphatase that constitutively inhibits basal activation of Fus3 and blocks activation of the mating pathway. These findings reveal the versatility of scaffolds and how a single MAPK cascade mediates different outputs.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Andersson
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.forename: Maosong
authors.initials: M
authors.lastname: Qi
authors.forename: Yunmei
authors.initials: Y
authors.lastname: Wang
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Elion
mesh_terms: D020001:1-Butanol / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing / Q000187:drug effects / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation; D019084:Fluorescent Antibody Technique, Indirect; D005656:Fungal Proteins / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D005656:Fungal Proteins; D044387:GTP-Binding Protein beta Subunits; C080321:STE5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C067576:Ste4 protein, S cerevisiae; D020001:1-Butanol; C075580:FUS3 protein, S cerevisiae; C541984:KSS1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C085791:MSG5 protein, S cerevisiae; D017027:Protein Tyrosine Phosphatases