Comparative analysis of HOG pathway proteins to generate hypotheses for functional analysis

Krantz, Marcus; Becit, Evren; Hohmann, Stefan

doi:10.1007/s00294-005-0039-9

Cited by 47 publications

(34 citation statements)

References 74 publications

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“…Our results also provide experimental support for a functional specialization of this branch in filamentous fungi, as recently suggested (43,44). Such a scenario is in agreement with recent results that show how changes in turgor in S. cerevisiae activate the HOG pathway via the SLN1 and not the SHO1 branch (74) and that in C. albicans Ssk2 is the only MAPKKK signaling to Hog1 (13).…”

Section: Discussionsupporting

confidence: 81%

Msb2 Signaling Mucin Controls Activation of Cek1 Mitogen-Activated Protein Kinase in Candida albicans

et al. 2009

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We have characterized the role that the Msb2 protein plays in the fungal pathogen Candida albicans by the use of mutants defective in the putative upstream components of the HOG pathway. Msb2, in cooperation with Sho1, controls the activation of the Cek1 mitogen-activated protein kinase under conditions that damage the cell wall, thus defining Msb2 as a signaling element of this pathway in the fungus. Candida albicans is an important human fungal pathogen, causing infections that may represent a serious health problem. This yeast is found as a commensal in certain body locations (mainly, the vagina and tractointestinal duct) but is able to gain access to different organs under conditions of altered host immune defenses causing severe diseases. Dimorphism, the environmentally regulated differentiation program that allows this fungus to switch between a yeast-like-form (unicellular) and a filamentous form (multicellular) (25,59,95), is considered to play an important-albeit not exclusive-role (27,51,79,82,94) in the virulence of this fungus. Therefore, besides its clinical importance as an opportunistic pathogen, this microbe represents an interesting model of morphogenesis and differentiation in lower eukaryotes.

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Section: Discussionsupporting

confidence: 81%

Msb2 Signaling Mucin Controls Activation of Cek1 Mitogen-Activated Protein Kinase in Candida albicans

et al. 2009

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“…Our results point to a second aspect of this relationship: Sko1 undergoes Hog1-dependent phosphorylation after osmotic stress. Hog1 may phosphorylate Sko1 directly, as known for the S. cerevisiae orthologues, because the ScSko1 phosphoacceptor sequence is well conserved in C. albicans Sko1 (Krantz et al, 2006). Indeed, sko1⌬/⌬ mutants are slightly sensitive to osmotic stress (our unpublished results), so these modes of Sko1 regulation may be functionally significant.…”

Section: Conservation Of the Hog1-sko1 Relationshipmentioning

confidence: 83%

Regulation of theCandida albicansCell Wall Damage Response by Transcription Factor Sko1 and PAS Kinase Psk1

Rauceo

Blankenship

Fanning

et al. 2008

MBoC

104

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The environmental niche of each fungus places distinct functional demands on the cell wall. Hence cell wall regulatory pathways may be highly divergent. We have pursued this hypothesis through analysis of Candida albicans transcription factor mutants that are hypersensitive to caspofungin, an inhibitor of beta-1,3-glucan synthase. We report here that mutations in SKO1 cause this phenotype. C. albicans Sko1 undergoes Hog1-dependent phosphorylation after osmotic stress, like its Saccharomyces cerevisiae orthologues, thus arguing that this Hog1-Sko1 relationship is conserved. However, Sko1 has a distinct role in the response to cell wall inhibition because 1) sko1 mutants are much more sensitive to caspofungin than hog1 mutants; 2) Sko1 does not undergo detectable phosphorylation in response to caspofungin; 3) SKO1 transcript levels are induced by caspofungin in both wild-type and hog1 mutant strains; and 4) sko1 mutants are defective in expression of caspofungin-inducible genes that are not induced by osmotic stress. Upstream Sko1 regulators were identified from a panel of caspofungin-hypersensitive protein kinase-defective mutants. Our results show that protein kinase Psk1 is required for expression of SKO1 and of Sko1-dependent genes in response to caspofungin. Thus Psk1 and Sko1 lie in a newly described signal transduction pathway.

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“…We find that signal transduction through the branch with the phospho-relay is more than twice as fast as the SHO1 branch employing an enzymatic cascade. Interestingly in some other yeasts and fungi, the Sho1 protein is not conserved or the SHO1 branch does not signal to the HOG pathway (6,(19)(20)(21). Furthermore, it is the faster SLN1 branch that is conserved in fungi.…”

Section: ϫ3mentioning

confidence: 99%

Signal processing by the HOG MAP kinase pathway

Hersen

McClean

Mahadevan

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

247

287

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Signaling pathways relay information about changes in the external environment so that cells can respond appropriately. How much information a pathway can carry depends on its bandwidth. We designed a microfluidic device to reliably change the environment of single cells over a range of frequencies. Using this device, we measured the bandwidth of the Saccharomyces cerevisiae signaling pathway that responds to high osmolarity. This prototypical pathway, the HOG pathway, is shown to act as a low-pass filter, integrating the signal when it changes rapidly and following it faithfully when it changes more slowly. We study the dependence of the pathway's bandwidth on its architecture. We measure previously unknown bounds on all of the in vivo reaction rates acting in this pathway. We find that the two-component Ssk1 branch of this pathway is capable of fast signal integration, whereas the kinase Ste11 branch is not. Our experimental techniques can be applied to other signaling pathways, allowing the measurement of their in vivo kinetics and the quantification of their information capacity.bandwidth ͉ HOG pathway ͉ microfluidics ͉ signal transduction F or a signaling pathway to carry accurate information about its environment, the output of the pathway must closely follow the input. Pathways measuring stimuli that change more rapidly with time need to carry more information. The information capacity of a pathway, i.e., how much information can be transmitted through the pathway per unit time, is proportional to the bandwidth of the pathway (1). The larger the bandwidth of a signaling pathway, the shorter its response time and the more accurately it can follow a rapidly varying signal. Bandwidth measurements are routinely used to characterize communications systems. In this article, we present an experimental technique combined with a microfluidic device that allows measurement of signaling-pathway bandwidth. We use this technique to measure the in vivo bandwidth of the hyperosmolar signaling pathway (HOG) in the yeast Saccharomyces cerevisiae (Fig. 1A).Signaling pathways consist of cascades of proteins where each protein activates the next (2). A signaling cascade is triggered when a receptor is activated by an external stimulus. Often, the signals are transmitted through kinase-dependent phosphorylation (Fig. 1 A). Information about the environment is then transmitted through the pathway, resulting in a response from the cell. The bandwidth of the pathway can be determined by measuring the response of the pathway to the input signal fluctuating at different frequencies. At frequencies up to the bandwidth, the pathway responds faithfully to the input stimulus. To understand how a signaling pathway responds to excitation over a range of frequencies, we numerically studied (3) the three-level branched signaling cascade shown in Fig. 1B and described in Box 1. When the input stimulus to this pathway oscillates at frequencies lower than the bandwidth b , the output of the cascade measured by the levels of the activated en...

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Comparative analysis of HOG pathway proteins to generate hypotheses for functional analysis

Cited by 47 publications

References 74 publications

Msb2 Signaling Mucin Controls Activation of Cek1 Mitogen-Activated Protein Kinase in Candida albicans

Msb2 Signaling Mucin Controls Activation of Cek1 Mitogen-Activated Protein Kinase in Candida albicans

Regulation of theCandida albicansCell Wall Damage Response by Transcription Factor Sko1 and PAS Kinase Psk1

Signal processing by the HOG MAP kinase pathway

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