Comprehensive analysis of aspergillus nidulans PKA phosphorylome identifies a novel mode of CreA regulation
Date
2019Journal
mBioPublisher
American Society for MicrobiologyType
Article
Metadata
Show full item recordAbstract
In filamentous fungi, an important kinase responsible for adaptation to changes in available nutrients is cyclic AMP (cAMP)-dependent protein kinase (protein kinase A [PKA]). This kinase has been well characterized at a molecular level, but its systemic action and direct/indirect targets are generally not well understood in filamentous fungi. In this work, we used a pkaA deletion strain (?pkaA) to identify Aspergillus nidulans proteins for which phosphorylation is dependent (either directly or indirectly) on PKA. A combination of phosphoproteomic and transcriptomic analyses revealed both direct and indirect targets of PKA and provided a global perspective on its function. One of these targets was the transcription factor CreA, the main repressor responsible for carbon catabolite repression (CCR). In the ?pkaA strain, we identified a previously unreported phosphosite in CreA, S319, which (based on motif analysis) appears to be a direct target of Stk22 kinase (AN5728). Upon replacement of CreA S319 with an alanine (i.e., phosphonull mutant), the dynamics of CreA import to the nucleus are affected. Collectively, this work provides a global overview of PKA function while also providing novel insight regarding significance of a specific PKA-mediated phosphorylation event. IMPORTANCE The cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling pathway is well conserved across eukaryotes, and previous work has shown that it plays an important role in regulating development, growth, and virulence in a number of fungi. PKA is activated in response to extracellular nutrients and acts to regulate metabolism and growth. While a number of components in the PKA pathway have been defined in filamentous fungi, current understanding does not provide a global perspective on PKA function. Thus, this work is significant in that it comprehensively identifies proteins and functional pathways regulated by PKA in a model filamentous fungus. This information enhances our understanding of PKA action and may provide information on how to manipulate it for specific purposes. Copyright 2019 Ribeiro et al.Sponsors
This material is based upon work supported, in part, by the National Science Foundation under grants 1517309 and 1601935.Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065464463&doi=10.1128%2fmBio.02825-18&partnerID=40&md5=63d8065c501c8ea1eec5eb985d361ed0; http://hdl.handle.net/10713/10579ae974a485f413a2113503eed53cd6c53
10.1128/mBio.02825-18
Scopus Count
Collections
Related articles
- Carbon Catabolite Repression in Filamentous Fungi Is Regulated by Phosphorylation of the Transcription Factor CreA.
- Authors: de Assis LJ, Silva LP, Bayram O, Dowling P, Kniemeyer O, Krüger T, Brakhage AA, Chen Y, Dong L, Tan K, Wong KH, Ries LNA, Goldman GH
- Issue date: 2021 Jan 5
- CreA-independent carbon catabolite repression of cellulase genes by trimeric G-protein and protein kinase A in Aspergillus nidulans.
- Authors: Kunitake E, Li Y, Uchida R, Nohara T, Asano K, Hattori A, Kimura T, Kanamaru K, Kimura M, Kobayashi T
- Issue date: 2019 Aug
- Regulation of <i>Aspergillus nidulans</i> CreA-Mediated Catabolite Repression by the F-Box Proteins Fbx23 and Fbx47.
- Authors: de Assis LJ, Ulas M, Ries LNA, El Ramli NAM, Sarikaya-Bayram O, Braus GH, Bayram O, Goldman GH
- Issue date: 2018 Jun 19
- Diverse Regulation of the CreA Carbon Catabolite Repressor in Aspergillus nidulans.
- Authors: Ries LN, Beattie SR, Espeso EA, Cramer RA, Goldman GH
- Issue date: 2016 May
- The pkaB gene encoding the secondary protein kinase A catalytic subunit has a synthetic lethal interaction with pkaA and plays overlapping and opposite roles in Aspergillus nidulans.
- Authors: Ni M, Rierson S, Seo JA, Yu JH
- Issue date: 2005 Aug