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Stress-Activated Protein Kinases in Human Fungal Pathogens

Lookup NU author(s): Dr Alison Day, Professor Janet Quinn



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


The ability of fungal pathogens to survive hostile environments within the host depends on rapid and robust stress responses. Stress-activated protein kinase (SAPK) pathways are conserved MAPK signaling modules that promote stress adaptation in all eukaryotic cells, including pathogenic fungi. Activation of the SAPK occurs via the dual phosphorylation of conserved threonine and tyrosine residues within a TGY motif located in the catalytic domain. This induces the activation and nuclear accumulation of the kinase and the phosphorylation of diverse substrates, thus eliciting appropriate cellular responses. The Hog1 SAPK has been extensively characterized in the model yeast Saccharomyces cerevisiae. Here, we use this a platform from which to compare SAPK signaling mechanisms in three major fungal pathogens of humans, Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. Despite the conservation of SAPK pathways within these pathogenic fungi, evidence is emerging that their role and regulation has significantly diverged. However, consistent with stress adaptation being a common virulence trait, SAPK pathways are important pathogenicity determinants in all these major human pathogens. Thus, the development of drugs which target fungal SAPKs has the exciting potential to generate broad-acting antifungal treatments.

Publication metadata

Author(s): Day AM, Quinn J

Publication type: Review

Publication status: Published

Journal: Frontiers in Cellular and Infection Microbiology

Year: 2019

Volume: 9

Issue: 261

Online publication date: 17/07/2019

Acceptance date: 04/07/2019

ISSN (electronic): 2235-2988

Publisher: Frontiers


DOI: 10.3389/fcimb.2019.00261