STE20/PAKA Protein Kinase Gene Releases an Autoinhibitory Domain through Pre-mRNA Alternative Splicing in the Dermatophyte Trichophyton rubrum

• Published in: International journal of molecular sciences Vol. 19; no. 11; p. 3654
• Main Authors: Gomes, Eriston V, Bortolossi, Julio C, Sanches, Pablo R, Mendes, Niege S, Martinez-Rossi, Nilce M, Rossi, Antonio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-11-2018; MDPI
• Subjects: Alternative splicing; Amino acids; Binding sites; Caspase-3; Cdc42 protein; Domains; Environmental changes; enzyme activation; Fungi; Genes; Information processing; intron retention; Kinases; MAP kinase; MAPK; mRNA; Phosphorylation; Protein kinase; Proteins; Proteolysis; Rac1 protein; Retention; Signal transduction; signaling pathway; Splicing; STE/PAK kinase; Trichophyton rubrum; undecanoic acid; Virulence; Virulence factors; Trichophyton rubrum; enzyme activation; alternative splicing; signaling pathway; MAPK; undecanoic acid; STE/PAK kinase; intron retention
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19113654

Signaling pathways are highly diverse in filamentous fungi, allowing the cells to receive and process ambient information. Interaction of components from different pathways results in signaling networks. The mitogen-activated protein kinase (MAPK) pathway is dependent on phosphorylation that is accomplished by kinase proteins. Thus, the STE/PAK protein kinase family plays essential roles in MAPK signal transduction, regulating several cellular functions. The STE/PAK protein displays an autoinhibitory (Cdc42/Rac interactive binding-CRIB) domain on its N-terminal portion, which interacts with the C-terminal catalytic kinase domain. Based on current knowledge, for the STE/PAK kinase to be activated, molecular signals (e.g., interaction with the activated form of Rac1 and Cdc42 proteins) or proteolytic cleavage by caspase 3 is necessary. Both mechanisms release the kinase domain from the CRIB interaction. Here, we hypothesize a novel molecular mechanism for the activation of STE20/PAKA kinase in
based on an alternative pre-mRNA splicing process. Our data suggest that, because of the retention of intron 1 of this gene, it is theoretically possible that the translation of STE20/PAKA kinase will be free of its autoinhibitory CRIB domain. These findings indicate a rapid response system to environmental changes. Furthermore, STE20/PAKA may be a potential
virulence factor and an interesting target for new drugs against dermatophytes.