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Inhibitory and activating functions for MAPK Kss1 in the S. cerevisiae filamentous- growth signalling pathway

Nature volume 390, pages 85–88 (1997)Cite this article

Abstract

Mitogen-activated protein kinase (MAPK) cascades are conserved signalling modules that regulate responses to diverse extracellular stimuli, developmental cues and environmental stresses (reviewed in refs 1,2,3). A MAPK is phosphorylated and activated by a MAPK kinase (MAPKK), which is activated by an upstream protein kinase, such as Raf, Mos or a MAPKK kinase. Ste7, a MAPKK in the yeast Saccharomyces cerevisiae, is required for two developmental pathways: mating4 and invasive (filamentous) growth5,6. Kss1 and Fus3, the MAPK targets of Ste7, are required for mating7,8, but their role in invasive growth has been unclear. Because no other S. cerevisiae MAPK has been shown to function in invasive growth, it was proposed5,6,9 that Ste7 may have non-MAPK targets. We show instead that Kss1 is the principal target of Ste7 in the invasive-growth response in both haploids and diploids. We demonstrate further that Kss1 in its inactive form is a potent negative regulator of invasive growth. Ste7 acts to relieve this negative regulation by switching Kss1 from an inhibitor to an activator. These results indicate that this MAPK has a physiologically important function in its unactivated state. Comparison of normal and MAPK-deficient cells indicates that nitrogen starvation and activated Ras stimulate filamentous growth through both MAPK-independent and MAPK-dependent means.

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Figure 1: The Ste7 MAPKK is not required for haploid invasive growth.
Figure 2: Kss1 is a potent repressor of haploid invasive growth.
Figure 3: Stimulatory and inhibitory functions of Kss1 are separable.
Figure 4: Ste7 and Kss1 potentiate, but are not required for, diploid pseudohyphal development in response to nutrient deprivation or activated Ras.
Figure 5: Model for regulation of haploid invasive growth and diploid pseudohyphal development by the Ste11–Ste7–Kss1 (and Fus3) MAPK cascade.

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Acknowledgements

We thank D. Voora for technical assistance with the data shown in Fig. 1e, and G. R. Fink for reagents. This work was supported by an NIH–NIGMS predoctoral traineeship and an NIH-NCI postdoctoral traineeship (to J.G.C.), an NIH-NCI postdoctoral traineeship and a senior postdoctoral fellowship from the Leukemia Society of America (to L.B.), an NIH-NIGMS research grant (to J.T.) and resources provided by the Berkeley campus Cancer Research Laboratory.

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Author notes

  1. Jeanette Gowen Cook, Lee Bardwell and Jeremy Thorner: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, 94720-3202, California, USA

    Jeremy Thorner

  2. Department of Genetics, Duke University Medical Center, Box 3054, Durham, 27710, North Carolina, USA

    Jeanette Gowen Cook

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  1. Jeanette Gowen Cook
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  2. Lee Bardwell
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  3. Jeremy Thorner
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Correspondence to Jeremy Thorner.

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Cook, J., Bardwell, L. & Thorner, J. Inhibitory and activating functions for MAPK Kss1 in the S. cerevisiae filamentous- growth signalling pathway. Nature 390, 85–88 (1997). https://doi.org/10.1038/36355

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