Comprehensive Analysis of <named-content content-type="genus-species">Aspergillus nidulans</named-content> PKA Phosphorylome Identifies a Novel Mode of CreA Regulation

ABSTRACT 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 ar...

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Autores principales:	Liliane F. C. Ribeiro, Cynthia Chelius, Karthik R. Boppidi, Nisha S. Naik, Simin Hossain, Jessica J. J. Ramsey, Jyothi Kumar, Lucas F. Ribeiro, Marc Ostermeier, Bao Tran, Young Ah Goo, Leandro J. de Assis, Mevlut Ulas, Ozgur Bayram, Gustavo H. Goldman, Stephen Lincoln, Ranjan Srivastava, Steven D. Harris, Mark R. Marten
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	CreA phosphoproteomic phosphosite signal transduction transcriptomic Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9ee07479ba274071800d77d21b2bee63
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spelling	oai:doaj.org-article:9ee07479ba274071800d77d21b2bee632021-11-15T15:55:25ZComprehensive Analysis of <named-content content-type="genus-species">Aspergillus nidulans</named-content> PKA Phosphorylome Identifies a Novel Mode of CreA Regulation10.1128/mBio.02825-182150-7511https://doaj.org/article/9ee07479ba274071800d77d21b2bee632019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02825-18https://doaj.org/toc/2150-7511ABSTRACT 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 (ΔpkaA) 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 ΔpkaA 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.Liliane F. C. RibeiroCynthia CheliusKarthik R. BoppidiNisha S. NaikSimin HossainJessica J. J. RamseyJyothi KumarLucas F. RibeiroMarc OstermeierBao TranYoung Ah GooLeandro J. de AssisMevlut UlasOzgur BayramGustavo H. GoldmanStephen LincolnRanjan SrivastavaSteven D. HarrisMark R. MartenAmerican Society for MicrobiologyarticleCreAphosphoproteomicphosphositesignal transductiontranscriptomicMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	CreA phosphoproteomic phosphosite signal transduction transcriptomic Microbiology QR1-502
spellingShingle	CreA phosphoproteomic phosphosite signal transduction transcriptomic Microbiology QR1-502 Liliane F. C. Ribeiro Cynthia Chelius Karthik R. Boppidi Nisha S. Naik Simin Hossain Jessica J. J. Ramsey Jyothi Kumar Lucas F. Ribeiro Marc Ostermeier Bao Tran Young Ah Goo Leandro J. de Assis Mevlut Ulas Ozgur Bayram Gustavo H. Goldman Stephen Lincoln Ranjan Srivastava Steven D. Harris Mark R. Marten Comprehensive Analysis of <named-content content-type="genus-species">Aspergillus nidulans</named-content> PKA Phosphorylome Identifies a Novel Mode of CreA Regulation
description	ABSTRACT 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 (ΔpkaA) 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 ΔpkaA 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.
format	article
author	Liliane F. C. Ribeiro Cynthia Chelius Karthik R. Boppidi Nisha S. Naik Simin Hossain Jessica J. J. Ramsey Jyothi Kumar Lucas F. Ribeiro Marc Ostermeier Bao Tran Young Ah Goo Leandro J. de Assis Mevlut Ulas Ozgur Bayram Gustavo H. Goldman Stephen Lincoln Ranjan Srivastava Steven D. Harris Mark R. Marten
author_facet	Liliane F. C. Ribeiro Cynthia Chelius Karthik R. Boppidi Nisha S. Naik Simin Hossain Jessica J. J. Ramsey Jyothi Kumar Lucas F. Ribeiro Marc Ostermeier Bao Tran Young Ah Goo Leandro J. de Assis Mevlut Ulas Ozgur Bayram Gustavo H. Goldman Stephen Lincoln Ranjan Srivastava Steven D. Harris Mark R. Marten
author_sort	Liliane F. C. Ribeiro
title	Comprehensive Analysis of <named-content content-type="genus-species">Aspergillus nidulans</named-content> PKA Phosphorylome Identifies a Novel Mode of CreA Regulation
title_short	Comprehensive Analysis of <named-content content-type="genus-species">Aspergillus nidulans</named-content> PKA Phosphorylome Identifies a Novel Mode of CreA Regulation
title_full	Comprehensive Analysis of <named-content content-type="genus-species">Aspergillus nidulans</named-content> PKA Phosphorylome Identifies a Novel Mode of CreA Regulation
title_fullStr	Comprehensive Analysis of <named-content content-type="genus-species">Aspergillus nidulans</named-content> PKA Phosphorylome Identifies a Novel Mode of CreA Regulation
title_full_unstemmed	Comprehensive Analysis of <named-content content-type="genus-species">Aspergillus nidulans</named-content> PKA Phosphorylome Identifies a Novel Mode of CreA Regulation
title_sort	comprehensive analysis of <named-content content-type="genus-species">aspergillus nidulans</named-content> pka phosphorylome identifies a novel mode of crea regulation
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/9ee07479ba274071800d77d21b2bee63
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Comprehensive Analysis of <named-content content-type="genus-species">Aspergillus nidulans</named-content> PKA Phosphorylome Identifies a Novel Mode of CreA Regulation

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