Abstract
Mitogen-activated protein kinases (MAPKs) are key mediators of signaling in fungi, participating in the response to diverse stresses and in developmental processes. Since the precise regulation of MAPKs is fundamental for cell physiology, fungi bear dual specificity phosphatases (DUSPs) that act as MAP kinase phosphatases (MKPs). Whereas fungal MKPs share characteristic domains of this phosphatase subfamily, they also have specific interaction motifs and particular activation mechanisms, which, for example, allow some yeast MKPs, such as Saccharomyces cerevisiae Sdp1, to couple oxidative stress with substrate recognition. Model yeasts show that MKPs play a key role in the modulation of MAPK signaling flow. Mutants affected in S. cerevisiae Msg5 or in Schizosaccharomyces pombe Pmp1 display MAPK hyperactivation and specific phenotypes. MKPs from virulent fungi, such as Candida albicans Cpp1, Fusarium graminearum Msg5, and Pyricularia oryzae Pmp1, are relevant for pathogenicity. Apart from transcriptional regulation, MKPs can be post-transcriptionally regulated by RNA-binding proteins such as Rnc1, which stabilizes the S. pombe PMP1 mRNA. P. oryzae Pmp1 activity and S. cerevisiae Msg5 stability are regulated by phosphorylation and ubiquitination, respectively. Therefore, fungi offer a platform to gain insight into the regulatory mechanisms that control MKPs.
Highlights
Mitogen-activated protein kinases (MAPKs) are key mediators of signaling in fungi, participating in the response to diverse stresses and in developmental processes
Cells perceive extracellular stimuli, such as hormones, mitogens, and growth factors, through surface receptors attached to the plasma membrane, which transduce the external signal to intracellular proteins. This signal converges in the activation of a MAPK module that is conserved in eukaryotic cells and whose function is the amplification of such signal by sequential events of phosphorylation, making this system sensitive to subtle changes in the cell environment
Understanding the functioning of MAPK cascades in these organisms is important since they are involved in the virulence of several human (e.g., Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus) and plant pathogens (e.g., Ustilago maydis, Pyricularia oryzae-sexual morph: Magnaporthe oryzae, and Ashbya gossypii) [7,8]
Summary
Cells communicate with the environment using an evolved machinery that allows them to interpret an external cue and translate it into an input message that permits the execution of cellular responses. Fungi process extracellular signals through MAPK cascades that conserve the architecture described above (Figure 1) These signaling pathways are specialized to face the different conditions that a fungus might encounter, such as high osmolarity concentrations, cell wall aggressions, mating pheromones, and, in certain cases, the presence of host factors or signals that trigger morphological transitions. The bridge (Cys47–Cys142 in Sdp and Cys80–Cys321 in Msg5) involves a cysteine located two residues downstream of the conserved catalytic cysteine within the active site and an upstream cysteine partner out of the catalytic domain (Figure 2) This disulfide bond is critical for optimal activity of these MKPs and participates in a molecular mechanism that couples oxidative stress with substrate recognition [28]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
