Redox Regulation, Rather than Stress-Induced Phosphorylation, of a Hog1 Mitogen-Activated Protein Kinase Modulates Its Nitrosative-Stress-Specific Outputs

Carmen Herrero de Dios, Alison M Day, Anna T Tillmann, Stavroula L Kastora, David Stead, Paula S. Salgado, Janet Quinn, Alistair J P Brown (Corresponding Author)

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Abstract

In all eukaryotic kingdoms, mitogen-activated protein kinases (MAPKs) play critical roles in cellular responses to environmental cues. These MAPKs are activated by phosphorylation at highly conserved threonine and tyrosine residues in response to specific inputs, leading to their accumulation in the nucleus and the activation of their downstream targets. A specific MAP kinase can regulate different downstream targets depending on the nature of the input signal, thereby raising a key question: what defines the stress-specific outputs of MAP kinases? We find that the Hog1 MAPK contributes to nitrosative-stress resistance in Candida albicans even though it displays minimal stress-induced phosphorylation under these conditions. We show that Hog1 becomes oxidized in response to nitrosative stress, accumulates in the nucleus, and regulates the nitrosative stress-induced transcriptome. Mutation of specific cysteine residues revealed that C156 and C161 function together to promote stress resistance, Hog1-mediated nitrosative-stress-induced gene expression, resistance to phagocytic killing, and C. albicans virulence. We propose that the oxidation of Hog1, rather than its phosphorylation, contributes to the nitrosative-stress-specific responses of this MAP kinase.
Original languageEnglish
Article numbere02229-17
JournalmBio
Volume9
Issue number2
Early online date27 Mar 2018
DOIs
Publication statusPublished - 2018

Keywords

  • MAP kinase signalling
  • Hog1
  • post-translational modification
  • nitrosative stress
  • transcript profiling
  • Candida albicans

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    Herrero de Dios, C., Day, A. M., Tillmann, A. T., Kastora, S. L., Stead, D., Salgado, P. S., Quinn, J., & Brown, A. J. P. (2018). Redox Regulation, Rather than Stress-Induced Phosphorylation, of a Hog1 Mitogen-Activated Protein Kinase Modulates Its Nitrosative-Stress-Specific Outputs. mBio, 9(2), [e02229-17]. https://doi.org/10.1128/mBio.02229-17