Dual Role for Membrane Localization in Yeast MAP Kinase Cascade Activation and Its Contribution to Signaling Fidelity

Lamson, Rachel E.; Takahashi, Satoe; Winters, Matthew J.; Pryciak, Peter M.

doi:10.1016/j.cub.2006.02.060

Cited by 52 publications

(63 citation statements)

References 30 publications

(89 reference statements)

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“…Dynamic scaffolding to allow assembly of protein complex on the membrane through multiple weak interactions may provide a flexible means for polarity regulation and adaptation to changing conditions. A similar mechanism has been proposed for Ste5 in MAPK signalling [121]. Studies of dynamic scaffolds in other fungal morphogenetic systems could lend further insights into their role as flexible linkages in the evolution of morphological diversity.…”

Section: Scaffolds As Potential Flexible Linkagessupporting

confidence: 54%

Yeast and fungal morphogenesis from an evolutionary perspective

Wedlich‐Söldner

2008

Seminars in Cell & Developmental Biology

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Cellular morphogenesis is a complex process and molecular studies in the last few decades have amassed a large amount of information that is difficult to grasp in any completeness. Fungal systems, in particular the budding and fission yeasts, have been important players in unravelling the basic structural and regulatory elements involved in a wide array of cellular processes. In this article, we address the design principles underlying the various processes of yeast and fungal morphogenesis. We attempt to explain the apparent molecular complexity from the perspective of the evolutionary theory of "facilitated variation". Following a summary of some of the most studied morphogenetic phenomena, we discuss, using recent examples, the underlying core processes and their associated "weak" regulatory linkages that bring about variation in morphogenetic phenotypes.

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Section: Scaffolds As Potential Flexible Linkagessupporting

confidence: 54%

Yeast and fungal morphogenesis from an evolutionary perspective

Wedlich‐Söldner

2008

Seminars in Cell & Developmental Biology

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“…Prior work suggested that reimport of Ste5 into the nucleus contributes to attenuation of pheromone-evoked signaling (53) and reduces inadvertent signaling in naïve cells (55,111). Our discovery that Ste5 degradation can occur only in the nucleus now provides a physiologically meaningful rationale for these findings.…”

Section: Discussionmentioning

confidence: 56%

Nucleus-Specific and Cell Cycle-Regulated Degradation of Mitogen-Activated Protein Kinase Scaffold Protein Ste5 Contributes to the Control of Signaling Competence

Garrenton

Braunwarth

Irniger

et al. 2009

Molecular and Cellular Biology

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Saccharomyces cerevisiae cells are capable of responding to mating pheromone only prior to their exit from the G 1 phase of the cell cycle. Ste5 scaffold protein is essential for pheromone response because it couples pheromone receptor stimulation to activation of the appropriate mitogen-activated protein kinase (MAPK) cascade. In naïve cells, Ste5 resides primarily in the nucleus. Upon pheromone treatment, Ste5 is rapidly exported from the nucleus and accumulates at the tip of the mating projection via its association with multiple plasma membrane-localized molecules. We found that concomitant with its nuclear export, the rate of Ste5 turnover is markedly reduced. Preventing nuclear export destabilized Ste5, whereas preventing nuclear entry stabilized Ste5, indicating that Ste5 degradation occurs mainly in the nucleus. This degradation is dependent on ubiquitin and the proteasome. We show that Ste5 ubiquitinylation is mediated by the SCF Cdc4 ubiquitin ligase and requires phosphorylation by the G 1 cyclin-dependent protein kinase (cdk1). The inability to efficiently degrade Ste5 resulted in pathway activation and cell cycle arrest in the absence of pheromone. These findings reveal that maintenance of this MAPK scaffold at an appropriately low level depends on its compartment-specific and cell cycle-dependent degradation. Overall, this mechanism provides a novel means for helping to prevent inadvertent stimulus-independent activation of a response and for restricting and maximizing the signaling competence of the cell to a specific cell cycle stage, which likely works hand in hand with the demonstrated role that G 1 Cdk1-dependent phosphorylation of Ste5 has in preventing its association with the plasma membrane.

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“…In step 1, Ste11 is activated by the Cdc42-dependent kinase Ste20 (or its paralog, Cla4). Ste20 phosphorylates the N-terminal inhibitory domain of Ste11 to unleash the catalytic activity of the C-terminal kinase domain (46). In step 2, the signal is amplified by enhancing the interaction between activated Ste11 and its substrate, Pbs2 (9).…”

Section: Discussionmentioning

confidence: 99%

Binding of the Extracellular Eight-Cysteine Motif of Opy2 to the Putative Osmosensor Msb2 Is Essential for Activation of the Yeast High-Osmolarity Glycerol Pathway

Yamamoto

Tatebayashi

Saito

2016

Molecular and Cellular Biology

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To adapt to environmental high osmolarity, the budding yeast Saccharomyces cerevisiae activates the Hog1 mitogen-activated protein kinase, which regulates diverse osmoadaptive responses. Hog1 is activated through the high-osmolarity glycerol (HOG) pathway, which consists of independent upstream signaling routes termed the SLN1 branch and the SHO1 branch. Here, we report that the extracellular cysteine-rich (CR) domain of the transmembrane-anchor protein Opy2 binds to the Hkr1-Msb2 homology (HMH) domain of the putative osmosensor Msb2 and that formation of the Opy2-Msb2 complex is essential for osmotic activation of Hog1 through the MSB2 subbranch of the SHO1 branch. By analyzing the phenotypes of mutants with Opy2 cysteine-to-alanine mutations, we deduced that the CR domain forms four intramolecular disulfide bonds. To probe for the potential induction of conformational changes in the Opy2-Msb2 complex by osmostress, we constructed mutants with a site-specific Cys-to-Ala mutation of the Opy2 CR domain and mutants with a Cys substitution of the Msb2 HMH domain. Each of these mutants had a reduced cysteine. These mutants were then combinatorially cross-linked using chemical cross-linkers of different lengths. Cross-linking between Opy2 Cys48 and Msb2 Cys1023 was sensitive to osmotic changes, suggesting that osmostress induced a conformational change. We therefore propose that the Opy2-Msb2 complex might serve as an osmosensor. Survival of living organisms depends on their ability to adapt to adverse environmental conditions. A well-known example is the response of the budding yeast Saccharomyces cerevisiae to high external osmolarity. When exposed to high osmolarity, yeast cells initiate a coordinated adaptive response that includes the synthesis and accumulation of the compatible osmolyte glycerol, changes in the global pattern of gene expression and protein synthesis, and a temporary arrest of cell cycle progression (1-3). These responses are controlled by the Hog1 mitogen-activated protein kinase (MAPK), which is activated via the high-osmolarity glycerol (HOG) signal pathway. The HOG pathway employs multiple and redundant routes between the input (external high osmolarity) and the output (Hog1-dependent responses). Specifically, the HOG pathway consists of two independent upstream signaling routes termed the SLN1 branch and the SHO1 branch (Fig. 1A). The osmosensor for the SLN1 branch is the sensor histidine kinase Sln1, which transmits the signal through a two-component phosphorelay mechanism to the redundant MAPK kinase kinases (MAPKKKs) Ssk2 and Ssk22 (4, 5). Ssk2/Ssk22 activates the Pbs2 MAPK kinase (MAPKK), which eventually activates the Hog1 MAPK (5-8).When the SLN1 branch is inactivated by the ssk2⌬ ssk22⌬ double mutation (here abbreviated ssk2/22⌬), yeast can still adapt to high osmolarity using the SHO1 branch. The major osmosensor for the SHO1 branch is the four-transmembrane (TM) protein Sho1 (5, 9). In the SHO1 branch, osmostress activates the Ste11 MAPKKK, which then sequentially activates Pbs2 an...

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Dual Role for Membrane Localization in Yeast MAP Kinase Cascade Activation and Its Contribution to Signaling Fidelity

Cited by 52 publications

References 30 publications

Yeast and fungal morphogenesis from an evolutionary perspective

Yeast and fungal morphogenesis from an evolutionary perspective

Nucleus-Specific and Cell Cycle-Regulated Degradation of Mitogen-Activated Protein Kinase Scaffold Protein Ste5 Contributes to the Control of Signaling Competence

Binding of the Extracellular Eight-Cysteine Motif of Opy2 to the Putative Osmosensor Msb2 Is Essential for Activation of the Yeast High-Osmolarity Glycerol Pathway

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