Mitogen-Activated Protein Kinase Phosphatases (MKPs) in Fungal Signaling: Conservation, Function, and Regulation.

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 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 Msg5 or in Pmp1 display MAPK hyperactivation and specific phenotypes. MKPs from virulent fungi, such as Cpp1, Msg5, and 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 mRNA. Pmp1 activity and Msg5 stability are regulated by phosphorylation and ubiquitination, respectively. Therefore, fungi offer a platform to gain insight into the regulatory mechanisms that control MKPs.