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

Autor(es)

Gomes, Eriston V. ; Bortolossi, Julio C. ; Sanches, Pablo R. ; Mendes, Niege S. ; Martinez-Rossi, Nilce M. ; Rossi, Antonio

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 19, n. 11, p. 11-pg., 2018-11-01.

Resumo

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 bindingCRIB) 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 Trichophyton rubrum 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 T. rubrum virulence factor and an interesting target for new drugs against dermatophytes. (AU)

• Processo FAPESP: 14/03847-7 - Caracterização molecular de mecanismos envolvidos na patogenicidade e sinalização celular em fungos
• Beneficiário: Nilce Maria Martinez-Rossi
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/04274-6 - Fatores de transcrição e sinalização celular
• Beneficiário: Eriston Vieira Gomes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado