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Vol. 19, Issue 3, 1113-1124, March 2008

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The Sequential Activation of the Yeast HOG and SLT2 Pathways Is Required for Cell Survival to Cell Wall Stress

Clara Bermejo^*,, Estefanía Rodríguez^*,,, Raúl García^*,, Jose M. Rodríguez-Peña^*, María L. Rodríguez de la Concepción, Carmen Rivas^*, Patricia Arias^*, César Nombela^*, Francesc Posas, and Javier Arroyo^*

*Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain; and Cell Signalling Unit, Department de Ciènces Experimentals I de la Salut, Universitat Pompeu Fabra (UPF), Parc de Recerca Biomèdica de Barcelona (PRBB), E-08003 Barcelona, Spain

Submitted August 2, 2007; Revised December 11, 2007; Accepted December 27, 2007
Monitoring Editor: Daniel Lew

Yeast mitogen-activated protein kinase (MAPK) signaling pathways transduce external stimuli into cellular responses very precisely. The MAPKs Slt2/Mpk1 and Hog1 regulate transcriptional responses of adaptation to cell wall and osmotic stresses, respectively. Unexpectedly, we observe that the activation of a cell wall integrity (CWI) response to the cell wall damage caused by zymolyase (β-1,3 glucanase) requires both the HOG and SLT2 pathways. Zymolyase activates both MAPKs and Slt2 activation depends on the Sho1 branch of the HOG pathway under these conditions. Moreover, adaptation to zymolyase requires essential components of the CWI pathway, namely the redundant MAPKKs Mkk1/Mkk2, the MAPKKK Bck1, and Pkc1, but it does not require upstream elements, including the sensors and the guanine nucleotide exchange factors of this pathway. In addition, the transcriptional activation of genes involved in adaptation to cell wall stress, like CRH1, depends on the transcriptional factor Rlm1 regulated by Slt2, but not on the transcription factors regulated by Hog1. Consistent with these findings, both MAPK pathways are essential for cell survival under these circumstances because mutant strains deficient in different components of both pathways are hypersensitive to zymolyase. Thus, a sequential activation of two MAPK pathways is required for cellular adaptation to cell wall damage.

These authors contributed equally to this work.

Present address: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1203, NY 10029.

Address correspondence to: Javier Arroyo (jarroyo{at}farm.ucm.es)