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| Subject Categories: Signal Transduction | Differentiation & Death |
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| The EMBO Journal
(2004) 23, 2564–2576, doi:10.1038/sj.emboj.7600250 Published online 10 June 2004 |
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| Differential input by Ste5 scaffold and Msg5 phosphatase route a MAPK cascade to multiple outcomes |
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| Jessica Andersson1, 2, David M Simpson2, Maosong Qi, Yunmei Wang and Elaine A Elion |
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA To whom correspondence should be addressed Elaine A Elion, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. Tel.: +1 617 432 3815; Fax: +1 617 738 0516; E-mail: elaine_elion@hms.harvard.edu 1 Present address: Ludwig Institute for Cancer Research, Nobels väg 3, 171 77 Stockholm, Sweden 2 These authors contributed equally to this work Received 25 February 2004; Accepted 4 May 2004; Published online 10 June 2004. |
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| Abstract |
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| 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. |
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| Keywords: Kss1, MAPK phosphatase, Msg5, Ste5 scaffold, Ste11 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHRegulated cell-to-cell variation in a cell-fate decision system Nature Article (29 Sep 2005) MAP kinase dynamics in response to pheromones in budding yeast Nature Cell Biology Article (01 Dec 2001) Nature Letters to Editor (06 Nov 1997) |
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