Skip to main page content

• HOME
• Current Issue
• Archive
• Alerts
• About ASM
• Contact us
• Tech Support
• Journals.ASM.org

This Article Abstract Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boisnard, S. Articles by Papon, N. Search for Related Content PubMed PubMed Citation Articles by Boisnard, S. Articles by Papon, N.

 Previous Article

Eukaryotic Cell, December 2008, p. 2179-2183, Vol. 7, No. 12
1535-9778/08/$08.00+0     doi:10.1128/EC.00262-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Insight into the Role of HOG Pathway Components Ssk2p, Pbs2p, and Hog1p in the Opportunistic Yeast Candida lusitaniae ^,

Stéphanie Boisnard, Gwenaël Ruprich-Robert, Martine Florent, Bruno Da Silva, Florence Chapeland-Leclerc, and Nicolas Papon^*

Programme Chimiorésistance des Levures Pathogènes, EA209 Eucaryotes Pathogènes: Transports Membranaires et Chimiorésistance, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, 75006 Paris, France

Received 4 August 2008/ Accepted 15 October 2008

Top ABSTRACT TEXT REFERENCES

 
In the present study, we have investigated the role of SSK2, PBS2, and HOG1, encoding modules of the high-osmolarity-glycerol mitogen-activated protein kinase pathway in Candida lusitaniae. Functional analysis of mutants indicated that Ssk2p, Pbs2p, and Hog1p are involved in osmotolerance, drug sensitivity, and heavy metal tolerance but not in oxidant stress adaptation.

Top ABSTRACT TEXT REFERENCES

 
One important component of the Saccharomyces cerevisiae signaling network is the high-osmolarity-glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway, which responds to osmotic, oxidative, and heavy metal stress (for reviews, see references 14 and 30). This transduction module also plays a broad role in regulating morphology, growth, and adaptation to various conditions in a number of other fungal species (1, 3, 7, 8, 10, 12, 13, 15-18, 20, 21, 25, 27, 32, 33, 35, 36). The HOG MAPK signaling pathway consists of MAPK Hog1p, MAPK kinase (MAPKK) Pbs2p, and MAPKK kinase (MAPKKK) Ssk2p, which communicate by a phosphorylation cascade. It is now accepted that the HOG pathway can be regulated by two upstream branches. The first branch is referred to as the two-component system and includes the histidine kinase receptor Sln1p, the histidine-containing phosphotransferase Ypd1p, and the response regulator Ssk1p. Ssk1p modulates the Ssk2p-Pbs2p-Hog1p activity by regulating the Ssk2p MAPKKK. The second branch is initiated by the Sho1p adaptor protein, which makes use of several proteins (Ste20p, Ste50p, and Ste11p) to link the HOG cascade through the Pbs2p MAPKK (31).

In two previous studies, we reported the characterization of genes (SLN1, NIK1, CHK1, YPD1, SSK1, and SKN7) encoding members of the two-component system in the opportunistic yeast Candida lusitaniae (5, 29). In the present study, we investigated the contribution of the downstream HOG MAPK pathway elements Ssk2p, Pbs2p, and Hog1p in the stress adaptation, drug sensitivity, mating ability, and yeast-to-pseudohyphae morphological transition of this fungal species.

The sequences of the C. lusitaniae SSK2 (CLUG_02562.1), PBS2 (CLUG_03729.1), and HOG1 (CLUG_01883.1) genes were retrieved from the annotated Candida database of the Broad Institute (http://www.broad.mit.edu/). To determine the role of these genes in C. lusitaniae, null mutants were constructed for each one by using the URA3 blaster strategy (5, 24) (see Fig. S1 in the supplemental material). All disruptant and reintegrant strains are listed in Table 1.

View this table: [in this window] [in a new window]

TABLE 1. Candida lusitaniae strains

We first investigated the putative involvement of Ssk2p, Pbs2p, and Hog1p in the integration and transduction of various environmental stress signals. For this purpose, we analyzed the growth, osmotolerance, oxidative stress response, drug sensitivity, and metalloid tolerance of the ssk2, pbs2, and hog1 mutants. All strains exhibited similar doubling times in liquid yeast extract-peptone-dextrose (YPD) medium (Table 1). Furthermore, no difference was observed in the growths (colony lengths and aspects) of the wild-type and mutant strains when the strains were cultured in solid YPD or yeast nitrogen base medium (data not shown). The growths of the ssk2, pbs2, and hog1 mutants are affected on high-osmolarity medium (1.5 M sorbitol, 1 M NaCl or KCl) (Fig. 1). Interestingly, we found that the ssk2 mutant is slightly less sensitive to these osmolytes than the pbs2 and hog1 mutants. However, these results indicate that C. lusitaniae Ssk2p, Pbs2p, and Hog1p could be involved in the capacity of adaptation of yeast cells to hyperosmotic conditions. All the strains tested (wild-type, mutant, and reintegrant strains) displayed similar phenotypes when grown under oxidant conditions (H₂O₂ or menadione). The three mutants exhibited hypersensitivity to UV irradiation (2,880 J m^–2) and high temperature (43°C), implying that Ssk2p, Pbs2p, and Hog1p are also essential for responses to these signals. Moreover, the ssk2, pbs2, and hog1 mutants were sensitive to methylglyoxal (30 mM), suggesting that HOG pathway components are required to protect cells from this metabolic by-product (2, 19). C. lusitaniae ssk2, pbs2, and hog1 cells displayed similarly increased resistance to the cell wall biogenesis inhibitor Congo red relative to wild-type cells. However, we found these mutants slightly sensitive to calcofluor white (a compound that interferes with cell wall formation) and to the purine analogue caffeine. Finally, the ssk2, pbs2, and hog1 mutants showed impaired growth on cadmium- or arsenite-containing media, suggesting a role for Ssk2p, Pbs2p, and Hog1p in the regulation of heavy metal detoxification (Fig. 1).

View larger version (37K): [in this window] [in a new window]

FIG. 1. Sensitivity of the wild-type strain; representative single mutants ssk2, pbs2, and hog1; and the reintegrant ssk2 + SSK2, pbs2 + PBS2, and hog1 + HOG1 strains to different stresses. All strains were grown overnight in YPD liquid medium, the cells were counted, and then dilutions (105 to 102 cells) were spotted onto a YPD plate supplemented or not supplemented (control) with 1.5 M sorbitol, 1 M NaCl or KCl, 8 mM H2O2, 100 µM menadione, 80 µg ml–1 calcofluor white, 200 µg ml–1 Congo red, 10 mM caffeine, 30 mM methylglyoxal, 4 µg ml–1 fenpiclonil, 12 µg ml–1 iprodione, 50 µM Cd(NO3)2, or 800 µM AsNaO2. To test UV sensitivity, cells on YPD plates were exposed to UV for 12 s (2,880 J m–2). Each plate was further incubated for 1 day at 35°C and photographed. For high-temperature sensitivity, spotted cells were incubated for 1 day at 43°C and photographed. This experiment was done in triplicate, and pictures show representative plates for each condition. WT, wild type.

In C. lusitaniae, mutation of NIK1 or SSK1, encoding histidine kinase receptor or response regulator proteins, respectively, leads to severe dicarboximide and phenylpyrrole resistance (5, 29). We thus tested if the deletion of genes encoding downstream elements could be responsible for a comparable antifungal sensitivity pattern. C. lusitaniae ssk2, pbs2, and hog1 cells displayed strong fenpiclonil and iprodione resistance (Fig. 1). Nevertheless, neither hypersensitivity nor resistance toward the clinical antifungals amphotericin B, 5-fuorocytosine, and fluconazole was observed (not shown). Therefore, we conclude that the HOG pathway modulates filamentous-fungus-specific antifungals (dicarboximides and phenylpyrroles) but not clinical antifungal susceptibility in C. lusitaniae.

We then investigated if the deletion of the SSK2, PBS2, or HOG1 genes could have an impact upon the in vitro mating ability of C. lusitaniae. Indeed, morphological changes occur during the sexual reproduction of C. lusitaniae, notably during conjugation (9). Genetic crosses were performed under the same conditions as those described previously, using the reference mating type tester strains 6936 (MATa) and CL38 (MAT) (9, 23). No variation in the number of conjugation tubes and produced tetrads (echinulate ascospores) was detected for any unilateral (ssk2 with CL38, pbs2 with CL38, or hog1 with CL38) or bilateral (ssk2 with ssk2, pbs2 with pbs2, or hog1 with hog1) genetic cross. Both groups of data indicate that Ssk2p, Pbs2p, and Hog1p do not participate in the mating process of C. lusitaniae.

C. lusitaniae can efficiently switch to pseudohyphal growth when cultured on solid medium depleted of a nitrogen source, such as yeast carbon base (YCB) (5, 11). Therefore, the capacity of mutants to differentiate pseudohyphae was investigated. For this purpose, approximately 10⁶ cells (in drops of 4 µl) of wild-type, ssk2, pbs2, and hog1 strains were spotted on various YCB solid media. Figure 2 shows representative pictures of pseudohyphae formation after 48 h of growth on YCB medium supplemented or not supplemented with a discriminatory concentration of each compound used in the drop plate assays described above. The concentrations indicated in Fig. 2 were used because higher and lower concentrations either were found too toxic or had no effect on the pseudohyphal development of the wild-type strain. The lengths of the pseudohyphae emerging from the edges of the colonies are reported in Table S2 in the supplemental material.

View larger version (73K): [in this window] [in a new window]

FIG. 2. Pseudohyphal-growth ability of mutants. Amounts of 106 cells (contained in drops of 4 µl) of the wild-type (WT) strain and representative mutants ssk2, pbs2, and hog1 were spotted onto YCB solid medium supplemented or not supplemented with a discriminatory concentration of sorbitol (0.8 M), NaCl (0.4 M), KCl (0.4 M), H2O2 (1 mM), menadione (60 µM), calcofluor white (50 µg ml–1), Congo red (100 µg ml–1), caffeine (1 mM), methylglyoxal (15 mM), iprodione (2 µg ml–1), fenpiclonil (0.5 µg ml–1), Cd(NO3)2 (25 µM), or AsNaO2 (500 µM). Pictures were taken 48 h after spotting. This experiment was done in triplicate, and pictures show representative structures observed for each sample. The lengths of the pseudohyphae emerging from the edges of the colonies are reported in Table S2 in the supplemental material. Bar, 300 µm.

Homogeneously distributed pseudohyphae of equivalent lengths were obtained for all four strains on unsupplemented YCB medium (Fig. 2). More precisely, morphogenesis per se was not altered, since the numbers of lateral cells branching along the pseudohyphae do not significantly differ between the mutants and the wild-type strain. Addition of 0.8 M sorbitol produced a homogeneous reduction of pseudohyphae growth of the wild-type strain and partially inhibited pseudohyphal development of ssk2. Similar results were observed in the presence of 0.4 M NaCl or KCl, in which ssk2 formed some sporadic bunch-like pseudohyphae (Fig. 2). The most important result of these experiments was that both mutants exhibited even stronger sensitivities to osmostress since the pseudohyphal growths of the pbs2 and hog1 strains were completely abolished on this high-osmolarity medium. These observations imply that Ssk2p, Pbs2p, and Hog1p likely play a role in osmotolerance during the pseudohyphal development of C. lusitaniae. A significant effect of methylglyoxal was also observed since the growths of the ssk2, pbs2, and hog1 mutants were restricted to bunch-like pseudohyphae, compared to the homogenous pseudohyphal formation of the wild type at the same concentration. As expected, although the switch of the wild-type strain was altered on YCB medium containing a discriminatory concentration of fenpiclonil or iprodione, the pseudohyphal developments of the ssk2, pbs2, and hog1 mutants were similar to those observed on drug-free YCB medium. The dicarboximide and phenylpyrrole resistance mediated by inactivation of HOG pathway components also occurred during the morphogenetic transition in C. lusitaniae. Finally, the effects of an oxidant (H₂O₂ or menadione), cell wall assembly inhibitors (Congo red and calcofluor white), caffeine, and metalloids on yeast cells, as detailed above, were also investigated on pseudohyphal formation. Strikingly, the mutants showed no significant reduction of pseudohyphal development in the presence of discriminatory concentrations of these compounds relative to the growth of the wild type (Fig. 2).

To summarize, the results obtained in this work strengthen the putative architecture of the C. lusitaniae two-component signaling pathway recently proposed (see reference 29; an update is provided in Fig. 3). Indeed, Ssk2p, Pbs2p, and Hog1p are clearly implicated in osmoadaptation, as reported for a large pallet of yeast and for filamentous-fungus models (3, 6, 12, 16, 26). In addition, the HOG MAPK components appear to be essential for UV and heat shock tolerance, as recently described for Cryptococcus neoformans (3). However, as suggested in a previous work, the Ssk1p-Ssk2p-Pb2p-Hog1p branch seems not to be required for oxidant adaptation in C. lusitaniae. In this way, the Sln1p-Ypd1p-Skn7p pathway likely takes charge of this function in C. lusitaniae (5, 29). Our data also provide evidence that the HOG pathway is involved in response to the heavy metals cadmium and arsenite, as recently reported for C. albicans and S. cerevisiae (6, 34). The present study (in addition to previous studies [5, 29]) supports the hypothesis that a Nik1p-Ypd1p-Ssk1p-Ssk2p-Pbs2p-Hog1p circuitry is probably crucial for dicarboximide and phenylpyrrole sensitivity (4, 16, 22).

View larger version (48K): [in this window] [in a new window]

FIG. 3. Putative model for the action of the two-component system in C. lusitaniae. A possible mechanism that incorporates our experimental results from this study and our previous studies (5, 29) is proposed. The HOG MAPK cascade could operate downstream of the Sln1p HKR, the HPt protein Ypd1p, and the Ssk1p response regulator to regulate the osmotic stress response, pseudohyphal growth, UV adaptation, the heat shock response, and the heavy metal tolerance. In addition, the Nik1p-Ypd1p-Ssk1p-Ssk2p-Pbs2p-Hog1p-mediated transduction pathway probably regulates dicarboximide (dicarb.) and phenylpyrrole (phenylp.) sensitivity. Genes encoding Sho1p, Cdc42p, Ste11p, Ste50p, and Ste20p (dotted boxes) are located in the C. lusitaniae genome (unpublished data), but it is likely that the Sho1p branch does not regulate the HOG MAPK cascade (see Fig. S2 in the supplemental material). It is possible that the HOG pathway could integrate signal from a novel osmotic-stress signaling branch, as recently proposed for C. albicans (6, 28). Dotted arrows indicate mechanisms or interactions not yet fully elucidated.

Preliminary experiments showed that the C. lusitaniae sho1 mutant does not display any strong overlapping stress-sensitive phenotypes exhibited by pbs2 and hog1 cells (see Fig. S2 in the supplemental material). These results thus suggested that in C. lusitaniae, Sho1p branch could not interact with the Pbs2p-Hog1p cascade. In this way, it is possible that the HOG pathway could integrate a signal from a novel osmotic-stress signaling module, as recently proposed for C. albicans (6, 28). Future investigations will aim to characterize the putative ability of the Sln1p, Nik1p, and Chk1p histidine kinase receptors to regulate the HOG cascade in this emerging pathogen.

 
We acknowledge the Broad Institute Fungal Genome Initiative for making the complete genome sequence of C. lusitaniae available. We thank Sandrine Castella, Heath Ecroyd, and Andrew J. Simkin for critical reading of the manuscript.

 
* Corresponding author. Mailing address: Programme Chimiorésistance des Levures Pathogènes, EA209 Eucaryotes Pathogènes: Transports Membranaires et Chimiorésistance, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, 4 avenue de l'Observatoire, 75006 Paris, France. Phone: (33) 1 53 73 96 42. Fax: (33) 1 53 73 96 40. E-mail: nicolas.papon{at}univ-paris5.fr

Published ahead of print on 24 October 2008.

Supplemental material for this article may be found at http://ec.asm.org/.

Top ABSTRACT TEXT REFERENCES

 

1
1. Adam, A. L., G. Kohut, and L. Hornok. 2008. Fphog1, a HOG-type MAP kinase gene, is involved in multistress response in Fusarium proliferatum. J. Basic Microbiol. 48:151-159.[Medline]
2
2. Aguilera, J., S. Rodriguez-Vargas, and J. A. Prieto. 2005. The HOG MAP kinase pathway is required for the induction of methylglyoxal-responsive genes and determines methylglyoxal resistance in Saccharomyces cerevisiae. Mol. Microbiol. 56:228-239.[CrossRef][Medline]
3
3. Bahn, Y. S., S. Geunes-Boyer, and J. Heitman. 2007. Ssk2 mitogen-activated protein kinase kinase kinase governs divergent patterns of the stress-activated Hog1 signaling pathway in Cryptococcus neoformans. Eukaryot. Cell 6:2278-2289.[Abstract/Free Full Text]
4
4. Bahn, Y. S., K. Kojima, G. M. Cox, and J. Heitman. 2006. A unique fungal two-component system regulates stress responses, drug sensitivity, sexual development, and virulence of Cryptococcus neoformans. Mol. Biol. Cell 17:3122-3135.[Abstract/Free Full Text]
5
5. Chapeland-Leclerc, F., P. Paccallet, G. Ruprich-Robert, D. Reboutier, C. Chastin, and N. Papon. 2007. Differential involvement of histidine kinase receptors in pseudohyphal development, stress adaptation, and drug sensitivity of the opportunistic yeast Candida lusitaniae. Eukaryot. Cell 6:1782-1794.[Abstract/Free Full Text]
6
6. Cheetham, J., D. A. Smith, A. da Silva Dantas, K. S. Doris, M. J. Patterson, C. R. Bruce, and J. Quinn. 2007. A single MAPKKK regulates the Hog1 MAPK pathway in the pathogenic fungus Candida albicans. Mol. Biol. Cell 18:4603-4614.[Abstract/Free Full Text]
7
7. Delgado-Jarana, J., S. Sousa, F. Gonzalez, M. Rey, and A. Llobell. 2006. ThHog1 controls the hyperosmotic stress response in Trichoderma harzianum. Microbiology 152:1687-1700.[Abstract/Free Full Text]
8
8. Du, C., J. Sarfati, J. P. Latge, and R. Calderone. 2006. The role of the sakA (Hog1) and tcsB (sln1) genes in the oxidant adaptation of Aspergillus fumigatus. Med. Mycol. 44:211-218.[CrossRef][Medline]
9
9. François, F., T. Noël, R. Pépin, A. Brulfert, C. Chastin, A. Favel, and J. Villard. 2001. Alternative identification test relying upon sexual reproductive abilities of Candida lusitaniae strains isolated from hospitalized patients. J. Clin. Microbiol. 39:3906-3914.[Abstract/Free Full Text]
10
10. Furukawa, K., Y. Hoshi, T. Maeda, T. Nakajima, and K. Abe. 2005. Aspergillus nidulans HOG pathway is activated only by two-component signalling pathway in response to osmotic stress. Mol. Microbiol. 56:1246-1261.[CrossRef][Medline]
11
11. Goumar, A., A. Brulfert, C. Martin, J. Villard, and T. Noël. 2004. Selection and genetic analysis of pseudohyphae defective mutants with attenuated virulence in Candida lusitaniae. J. Med. Mycol. 14:3-11.
12
12. Gregori, C., C. Schuller, A. Roetzer, T. Schwarzmuller, G. Ammerer, and K. Kuchler. 2007. The high-osmolarity glycerol response pathway in the human fungal pathogen Candida glabrata strain ATCC 2001 lacks a signaling branch that operates in baker's yeast. Eukaryot. Cell 6:1635-1645.[Abstract/Free Full Text]
13
13. Hernandez-Lopez, M. J., F. Randez-Gil, and J. A. Prieto. 2006. Hog1 mitogen-activated protein kinase plays conserved and distinct roles in the osmotolerant yeast Torulaspora delbrueckii. Eukaryot. Cell 5:1410-1419.[Abstract/Free Full Text]
14
14. Hohmann, S., M. Krantz, and B. Nordlander. 2007. Yeast osmoregulation. Methods Enzymol. 428:29-45.[CrossRef][Medline]
15
15. Iwaki, T., Y. Tamai, and Y. Watanabe. 1999. Two putative MAP kinase genes, ZrHOG1 and ZrHOG2, cloned from the salt-tolerant yeast Zygosaccharomyces rouxii are functionally homologous to the Saccharomyces cerevisiae HOG1 gene. Microbiology 145:241-248.[Abstract/Free Full Text]
16
16. Jones, C. A., S. E. Greer-Phillips, and K. A. Borkovich. 2007. The response regulator RRG-1 functions upstream of a mitogen-activated protein kinase pathway impacting asexual development, female fertility, osmotic stress, and fungicide resistance in Neurospora crassa. Mol. Biol. Cell 18:2123-2136.[Abstract/Free Full Text]
17
17. Kojima, K., Y. Takano, A. Yoshimi, C. Tanaka, T. Kikuchi, and T. Okuno. 2004. Fungicide activity through activation of a fungal signalling pathway. Mol. Microbiol. 53:1785-1796.[CrossRef][Medline]
18
18. Lenassi, M., T. Vaupotic, N. Gunde-Cimerman, and A. Plemenitas. 2007. The MAP kinase HwHog1 from the halophilic black yeast Hortaea werneckii: coping with stresses in solar salterns. Saline Systems 3:3.[CrossRef][Medline]
19
19. Maeta, K., S. Izawa, and Y. Inoue. 2005. Methylglyoxal, a metabolite derived from glycolysis, functions as a signal initiator of the high osmolarity glycerol-mitogen-activated protein kinase cascade and calcineurin/Crz1-mediated pathway in Saccharomyces cerevisiae. J. Biol. Chem. 280:253-260.[Abstract/Free Full Text]
20
20. Monge, R. A., E. Roman, C. Nombela, and J. Pla. 2006. The MAP kinase signal transduction network in Candida albicans. Microbiology 152:905-912.[Abstract/Free Full Text]
21
21. Moriwaki, A., E. Kubo, S. Arase, and J. Kihara. 2006. Disruption of SRM1, a mitogen-activated protein kinase gene, affects sensitivity to osmotic and ultraviolet stressors in the phytopathogenic fungus Bipolaris oryzae. FEMS Microbiol. Lett. 257:253-261.[CrossRef][Medline]
22
22. Motoyama, T., T. Ohira, K. Kadokura, A. Ichiishi, M. Fujimura, I. Yamaguchi, and T. Kudo. 2005. An Os-1 family histidine kinase from a filamentous fungus confers fungicide-sensitivity to yeast. Curr. Genet. 47:298-306.[CrossRef][Medline]
23
23. Noël, T., A. Favel, A. Michel-Nguyen, A. Goumar, K. Fallague, C. Chastin, F. Leclerc, and J. Villard. 2005. Differentiation between atypical isolates of Candida lusitaniae and Candida pulcherrima by determination of mating type. J. Clin. Microbiol. 43:1430-1432.[Abstract/Free Full Text]
24
24. Papon, N., T. Noel, M. Florent, S. Gibot-Leclerc, D. Jean, C. Chastin, J. Villard, and F. Chapeland-Leclerc. 2007. Molecular mechanism of flucytosine resistance in Candida lusitaniae: contribution of the FCY2, FCY1, and FUR1 genes to 5-fluorouracil and fluconazole cross-resistance. Antimicrob. Agents Chemother. 51:369-371.[Abstract/Free Full Text]
25
25. Park, S. M., E. S. Choi, M. J. Kim, B. J. Cha, M. S. Yang, and D. H. Kim. 2004. Characterization of HOG1 homologue, CpMK1, from Cryphonectria parasitica and evidence for hypovirus-mediated perturbation of its phosphorylation in response to hypertonic stress. Mol. Microbiol. 51:1267-1277.[CrossRef][Medline]
26
26. Posas, F., and H. Saito. 1997. Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK. Science 276:1702-1705.[Abstract/Free Full Text]
27
27. Ramamoorthy, V., X. Zhao, A. K. Snyder, J. R. Xu, and D. M. Shah. 2007. Two mitogen-activated protein kinase signalling cascades mediate basal resistance to antifungal plant defensins in Fusarium graminearum. Cell. Microbiol. 9:1491-1506.[CrossRef][Medline]
28
28. Román, E., C. Nombela, and J. Pla. 2005. The Sho1 adaptor protein links oxidative stress to morphogenesis and cell wall biosynthesis in the fungal pathogen Candida albicans. Mol. Cell. Biol. 25:10611-10627.[Abstract/Free Full Text]
29
29. Ruprich-Robert, G., F. Chapeland-Leclerc, S. Boisnard, M. Florent, G. Bories, and N. Papon. 2008. Contributions of the response regulators Ssk1p and Skn7p in the pseudohyphal development, stress adaptation, and drug sensitivity of the opportunistic yeast Candida lusitaniae. Eukaryot. Cell 7:1071-1074.[Abstract/Free Full Text]
30
30. Saito, H., and K. Tatebayashi. 2004. Regulation of the osmoregulatory HOG MAPK cascade in yeast. J. Biochem. 136:267-272.[Abstract/Free Full Text]
31
31. Seet, B. T., and T. Pawson. 2004. MAPK signaling: Sho business. Curr. Biol. 14:R708-R710.[CrossRef][Medline]
32
32. Segmüller, N., U. Ellendorf, B. Tudzynski, and P. Tudzynski. 2007. BcSAK1, a stress-activated mitogen-activated protein kinase, is involved in vegetative differentiation and pathogenicity in Botrytis cinerea. Eukaryot. Cell 6:211-221.[Abstract/Free Full Text]
33
33. Shiozaki, K., and P. Russell. 1996. Conjugation, meiosis, and the osmotic stress response are regulated by Spc1 kinase through Atf1 transcription factor in fission yeast. Genes Dev. 10:2276-2288.[Abstract/Free Full Text]
34
34. Sotelo, J., and M. A. Rodriguez-Gabriel. 2006. Mitogen-activated protein kinase Hog1 is essential for the response to arsenite in Saccharomyces cerevisiae. Eukaryot. Cell 5:1826-1830.[Abstract/Free Full Text]
35
35. Yoshimi, A., K. Kojima, Y. Takano, and C. Tanaka. 2005. Group III histidine kinase is a positive regulator of Hog1-type mitogen-activated protein kinase in filamentous fungi. Eukaryot. Cell 4:1820-1828.[Abstract/Free Full Text]
36
36. Zhang, Y., R. Lamm, C. Pillonel, S. Lam, and J. R. Xu. 2002. Osmoregulation and fungicide resistance: the Neurospora crassa os-2 gene encodes a HOG1 mitogen-activated protein kinase homologue. Appl. Environ. Microbiol. 68:532-538.[Abstract/Free Full Text]

---

Eukaryotic Cell, December 2008, p. 2179-2183, Vol. 7, No. 12
1535-9778/08/$08.00+0     doi:10.1128/EC.00262-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Fuchs, B. B., Mylonakis, E. (2009). Our Paths Might Cross: the Role of the Fungal Cell Wall Integrity Pathway in Stress Response and Cross Talk with Other Stress Response Pathways. Eukaryot Cell 8: 1616-1625 [Abstract] [Full Text]  
• Ko, Y.-J., Yu, Y. M., Kim, G.-B., Lee, G.-W., Maeng, P. J., Kim, S., Floyd, A., Heitman, J., Bahn, Y.-S. (2009). Remodeling of Global Transcription Patterns of Cryptococcus neoformans Genes Mediated by the Stress-Activated HOG Signaling Pathways. Eukaryot Cell 8: 1197-1217 [Abstract] [Full Text]  

This Article Abstract Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boisnard, S. Articles by Papon, N. Search for Related Content PubMed PubMed Citation Articles by Boisnard, S. Articles by Papon, N.