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Review
, 62 (4), 1264-300

MAP Kinase Pathways in the Yeast Saccharomyces Cerevisiae

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Review

MAP Kinase Pathways in the Yeast Saccharomyces Cerevisiae

M C Gustin et al. Microbiol Mol Biol Rev.

Abstract

A cascade of three protein kinases known as a mitogen-activated protein kinase (MAPK) cascade is commonly found as part of the signaling pathways in eukaryotic cells. Almost two decades of genetic and biochemical experimentation plus the recently completed DNA sequence of the Saccharomyces cerevisiae genome have revealed just five functionally distinct MAPK cascades in this yeast. Sexual conjugation, cell growth, and adaptation to stress, for example, all require MAPK-mediated cellular responses. A primary function of these cascades appears to be the regulation of gene expression in response to extracellular signals or as part of specific developmental processes. In addition, the MAPK cascades often appear to regulate the cell cycle and vice versa. Despite the success of the gene hunter era in revealing these pathways, there are still many significant gaps in our knowledge of the molecular mechanisms for activation of these cascades and how the cascades regulate cell function. For example, comparison of different yeast signaling pathways reveals a surprising variety of different types of upstream signaling proteins that function to activate a MAPK cascade, yet how the upstream proteins actually activate the cascade remains unclear. We also know that the yeast MAPK pathways regulate each other and interact with other signaling pathways to produce a coordinated pattern of gene expression, but the molecular mechanisms of this cross talk are poorly understood. This review is therefore an attempt to present the current knowledge of MAPK pathways in yeast and some directions for future research in this area.

Figures

FIG. 1
FIG. 1
MAPK cascades of S. cerevisiae. There are four MAPK pathways in vegetatively growing yeast and one, the spore wall assembly pathway, which is expressed only in sporulating yeast. Nomenclature for yeast genes and their products is as follows: STE20, gene name; ste20, recessive mutation; ste20Δ, deletion (usually null) mutation; and Ste20p, protein product of STE20. The question marks indicate that a protein kinase has not yet been identified for this step in a cascade. Note that each cascade has a unique MAPK. In addition, certain protein kinases act in more than one pathway: the MEK Ste7p (two pathways), the MEKK Ste11p (three pathways), and the upstream MAPK cascade activator kinase Ste20p (two pathways). The arrows represent known or postulated steps in signal transduction; see the text for details.
FIG. 2
FIG. 2
Pheromone response pathway of S. cerevisiae. The line with arrows connecting Gα to the GβGγ indicates the ability of the protein subunits to form a complex in the absence of pheromone. →, activation; ⊣, inhibition (these connections do not necessarily mean direct physical interactions). Proteins are labeled without the p suffix (e.g., Ste5 instead of Ste5p) to improve the legibility of the figure. See the text for details of signal transduction between different proteins on the pathway.
FIG. 3
FIG. 3
Filamentation-invasion pathway of S. cerevisiae. Symbols are as described in the legend to Fig. 2. See the text for details of signal transduction between different proteins on the pathway.
FIG. 4
FIG. 4
Cell integrity pathway of S. cerevisiae. This pathway appears to be regulated by several different signals listed at the top: nutrients, temperature, osmolarity, pheromone, and cyclin-dependent kinase (CDK). Where these different upstream signals feed in to the pathway is currently unknown. Whether Rlm1p and SBF mediate pathway regulation of separate (as shown) or overlapping sets of genes is not known.
FIG. 5
FIG. 5
HOG pathway of S. cerevisiae. The question marks show areas of uncertainty that require further investigation. Sln1p and Sho1p are assumed here to be present in the plasma membrane, but this has not yet been experimentally verified.
FIG. 6
FIG. 6
Three-component system of the HOG pathway. Phosphate is transferred from ATP to a histidine residue on the histidine kinase domain (octagon) of Sln1p and from there to an aspartate residue on the receiver domain (triangle) of a separate molecule of Sln1p. Whether phosphate can be transferred from the histidine kinase domain to a receiver domain on the same Sln1p polypeptide chain as the former remains to be determined. Phosphate is then transferred from Sln1p to the histidine kinase Ypd1p, to either of two receiver domain proteins Ssk1p or Skn7p, and then to water. The phospho and dephospho forms of Skn7p have different functions. The dephospho form of Ssk1p is an activator of the HOG pathway MEKKs Ssk2p and Ssk22p; the phospho form of Ssk1p has no known function.
FIG. 7
FIG. 7
Stress response pathway of S. pombe. Multiple stress signals activate the pathway, but the sensors for those signals have not yet been identified.
FIG. 8
FIG. 8
Spore wall assembly pathway of S. cerevisiae. Whether signaling in the pathway is modulated solely by expression of pathway proteins or whether an upstream activating physiological stimulus exists has not yet been determined. A MEKK and MEK for this pathway have not been identified, and so it remains an open question whether this is a typical three-kinase MAPK cascade.

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