Regulation of PKA activity by an autophosphorylation mechanism in <i>Saccharomyces cerevisiae</i>

Solari, Clara A.; Tudisca, Vanesa Romina; Pugliessi, Marcelo; Nadra, Alejandro D.; Moreno, Sílvia; Portela, Paula

doi:10.1042/bj20140577

Cited by 9 publications

(8 citation statements)

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“…The activity of Tpk1p is controlled by auto-phosphorylation on serine residues. Under starvation or glycerol-rich conditions, Tpk1p is de-phosphorylated [ 44 ] and CCR is released. To assess the translation and localization of PkaA in A. nidulans , the corresponding PkaA::GFP fusion was constructed.…”

Section: Resultsmentioning

confidence: 99%

Aspergillus nidulans protein kinase A plays an important role in cellulase production

Assis

Ries

Savoldi

et al. 2015

Biotechnol Biofuels

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BackgroundThe production of bioethanol from lignocellulosic feedstocks is dependent on lignocellulosic biomass degradation by hydrolytic enzymes. The main component of lignocellulose is cellulose and different types of organisms are able to secrete cellulases. The filamentous fungus Aspergillus nidulans serves as a model organism to study cellulase production and the available tools allow exploring more in depth the mechanisms governing cellulase production and carbon catabolite repression.ResultsIn A. nidulans, microarray data identified the cAMP-dependent protein kinase A (PkaA) as being involved in the transcriptional modulation and the production of lignocellulolytic enzymes in the presence of cellulose. Deletion of pkaA resulted in increased hydrolytic enzyme secretion, but reduced growth in the presence of lignocellulosic components and various other carbon sources. Furthermore, genes involved in fungal development were increased in the ΔpkaA strain, probably leading to the increased hyphal branching as was observed in this strain. This would allow the secretion of higher amounts of proteins. In addition, the expression of SynA, encoding a V-SNARE synaptobrevin protein involved in secretion, was increased in the ΔpkaA mutant. Deletion of pkaA also resulted in the reduced nuclear localization of the carbon catabolite repressor CreA in the presence of glucose and in partial de-repression when grown on cellulose. PkaA is involved in the glucose signaling pathway as the absence of this protein resulted in reduced glucose uptake and lower hexokinase/glucokinase activity, directing the cell to starvation conditions. Genome-wide transcriptomics showed that the expression of genes encoding proteins involved in fatty acid metabolism, mitochondrial function and in the use of cell storages was increased.ConclusionsThis study shows that PkaA is involved in hydrolytic enzyme production in A. nidulans. It appears that this protein kinase blocks the glucose pathway, hence forcing the cell to change to starvation conditions, increasing hydrolytic enzyme secretion and inducing the usage of cellular storages. This work uncovered new regulatory avenues governing the tight interplay between the metabolic states of the cell, which are important for the production of hydrolytic enzymes targeting lignocellulosic biomass. Deletion of pkaA resulted in a strain with increased hydrolytic enzyme secretion and reduced biomass formation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-015-0401-1) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Aspergillus nidulans protein kinase A plays an important role in cellulase production

Assis

Ries

Savoldi

et al. 2015

Biotechnol Biofuels

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“…Inactive PKA consists of two catalytical subunits (combinations of Tpk1p/2p/3p) that are being inhibited by two Bcy1p subunits [157]. As cAMP levels increase after signaling from Gpr1p and/or Ras1p/2p, cAMP promotes the autophosphorylation of the Tpk subunits (by a yet to be elucidated mechanism) which leads to their dissociation from the regulatory Bcy1p subunits, and the activation of PKA [157][158][159].…”

Section: Targets Induced/activated By Active Pkamentioning

confidence: 99%

D-Xylose Sensing in Saccharomyces cerevisiae: Insights from D-Glucose Signaling and Native D-Xylose Utilizers

Brink

Borgström

Persson

et al. 2021

IJMS

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Extension of the substrate range is among one of the metabolic engineering goals for microorganisms used in biotechnological processes because it enables the use of a wide range of raw materials as substrates. One of the most prominent examples is the engineering of baker’s yeast Saccharomyces cerevisiae for the utilization of d-xylose, a five-carbon sugar found in high abundance in lignocellulosic biomass and a key substrate to achieve good process economy in chemical production from renewable and non-edible plant feedstocks. Despite many excellent engineering strategies that have allowed recombinant S. cerevisiae to ferment d-xylose to ethanol at high yields, the consumption rate of d-xylose is still significantly lower than that of its preferred sugar d-glucose. In mixed d-glucose/d-xylose cultivations, d-xylose is only utilized after d-glucose depletion, which leads to prolonged process times and added costs. Due to this limitation, the response on d-xylose in the native sugar signaling pathways has emerged as a promising next-level engineering target. Here we review the current status of the knowledge of the response of S. cerevisiae signaling pathways to d-xylose. To do this, we first summarize the response of the native sensing and signaling pathways in S. cerevisiae to d-glucose (the preferred sugar of the yeast). Using the d-glucose case as a point of reference, we then proceed to discuss the known signaling response to d-xylose in S. cerevisiae and current attempts of improving the response by signaling engineering using native targets and synthetic (non-native) regulatory circuits.

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“…Several post-translational modifications on regulatory and catalytic subunits of yeast PKA affect its nuclear-cytoplasmic localization [55][56][57]. The transport mechanism of PKA subunits through nuclear membrane has not been previously characterized.…”

Section: Mechanism Of Nuclear Accumulation Of Pka In Response To Osmomentioning

confidence: 99%

PKA-chromatin association at stress responsive target genes from Saccharomyces cerevisiae

Baccarini

Martínez-Montañés

Rossi

et al. 2015

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Gene expression regulation by intracellular stimulus-activated protein kinases is essential for cell adaptation to environmental changes. There are three PKA catalytic subunits in Saccharomyces cerevisiae: Tpk1, Tpk2, and Tpk3 and one regulatory subunit: Bcy1. Previously, it has been demonstrated that Tpk1 and Tpk2 are associated with coding regions and promoters of target genes in a carbon source and oxidative stress dependent manner. Here we studied five genes, ALD6, SED1, HSP42, RPS29B, and RPL1B whose expression is regulated by saline stress. We found that PKA catalytic and regulatory subunits are associated with both coding regions and promoters of the analyzed genes in a stress dependent manner. Tpk1 and Tpk2 recruitment was completely abolished in catalytic inactive mutants. BCY1 deletion changed the binding kinetic to chromatin of each Tpk isoform and this strain displayed a deregulated gene expression in response to osmotic stress. In addition, yeast mutants with high PKA activity exhibit sustained association to target genes of chromatin-remodeling complexes such as Snf2-catalytic subunit of the SWI/SNF complex and Arp8-component of INO80 complex, leading to upregulation of gene expression during osmotic stress. Tpk1 accumulation in the nucleus was stimulated upon osmotic stress, while the nuclear localization of Tpk2 and Bcy1 showed no change. We found that each PKA subunit is transported into the nucleus by a different β-karyopherin pathway. Moreover, β-karyopherin mutant strains abolished the chromatin association of Tpk1 or Tpk2, suggesting that nuclear localization of PKA catalytic subunits is required for its association to target genes and properly gene expression.

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Regulation of PKA activity by an autophosphorylation mechanism in Saccharomyces cerevisiae

Cited by 9 publications

References 50 publications

Aspergillus nidulans protein kinase A plays an important role in cellulase production

Aspergillus nidulans protein kinase A plays an important role in cellulase production

D-Xylose Sensing in Saccharomyces cerevisiae: Insights from D-Glucose Signaling and Native D-Xylose Utilizers

PKA-chromatin association at stress responsive target genes from Saccharomyces cerevisiae

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