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dc.contributor.authorRibeiro, L.F.C.
dc.contributor.authorChelius, C.
dc.contributor.authorBoppidi, K.R.
dc.date.accessioned2019-09-13T14:49:30Z
dc.date.available2019-09-13T14:49:30Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85065464463&doi=10.1128%2fmBio.02825-18&partnerID=40&md5=63d8065c501c8ea1eec5eb985d361ed0
dc.identifier.urihttp://hdl.handle.net/10713/10579
dc.description.abstractIn 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.en_US
dc.description.sponsorshipThis material is based upon work supported, in part, by the National Science Foundation under grants 1517309 and 1601935.en_US
dc.description.urihttps://doi.org/10.1128/mBio.02825-18en_US
dc.language.isoen-USen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.ispartofmBio
dc.subjectCreAen_US
dc.subjectPhosphoproteomicen_US
dc.subjectPhosphositeen_US
dc.subjectSignal transductionen_US
dc.subjectTranscriptomicen_US
dc.titleComprehensive analysis of aspergillus nidulans PKA phosphorylome identifies a novel mode of CreA regulationen_US
dc.typeArticleen_US
dc.identifier.doi10.1128/mBio.02825-18
dc.identifier.pmid31040248


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