ArticleEukaryotic cell2005
Pde1 phosphodiesterase modulates cyclic AMP levels through a protein kinase A-mediated negative feedback loop in Cryptococcus neoformans.
Article in Eukaryotic cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 75 citations in OpenAlex.
- Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis.The Journal of clinical investigation · 2014Trial
- Pathogenic diversity ofCell surface (Amsterdam, Netherlands) · 2025Article
- Signaling Pathways Regulating Dimorphism in Medically Relevant Fungal Species.Pathogens (Basel, Switzerland) · 2025Review
- Leveraging a new data resource to define the response of Cryptococcus neoformans to environmental signals.Genetics · 2025Article
- Unbiased discovery of natural sequence variants that influence fungal virulence.Cell host & microbe · 2023Article
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- Campafungins: Inhibitors ofJournal of natural products · 2020Article
- Landscape of gene expression variation of natural isolates ofMicrobial genomics · 2020Article
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- Clonal Dispersal ofJournal of fungi (Basel, Switzerland) · 2019Article
- The cAMP/Protein Kinase a Pathway Regulates Virulence and Adaptation to Host Conditions inFrontiers in cellular and infection microbiology · 2019Review
- New findings on phosphodiesterases, MoPdeH and MoPdeL, in Magnaporthe oryzae revealed by structural analysis.Molecular plant pathology · 2018Article
- The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis.PLoS pathogens · 2018Article
- Role of the inositol pyrophosphate multikinase Kcs1 in Cryptococcus inositol metabolism.Fungal genetics and biology : FG & B · 2018Article
- Regulation of plant cell wall degradation by light inFungal biology and biotechnology · 2018Review
- Comparative Ecology of CapsularFrontiers in microbiology · 2017Article
- Virulence-Associated Enzymes of Cryptococcus neoformans.Eukaryotic cell · 2015Review
- Model-driven mapping of transcriptional networks reveals the circuitry and dynamics of virulence regulation.Genome research · 2015Article
- A Ric8/synembryn homolog promotes Gpa1 and Gpa2 activation to respectively regulate cyclic AMP and pheromone signaling in Cryptococcus neoformans.Eukaryotic cell · 2014Article
- Article
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3 authors.
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Abstract
The virulence of the human pathogenic fungus Cryptococcus neoformans is regulated by a cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling cascade that promotes mating and the production of melanin and capsule. In this study, genes encoding homologs of the Saccharomyces cerevisiae low- and high-affinity phosphodiesterases, PDE1 and PDE2, respectively, were deleted in serotype A strains of C. neoformans. The resulting mutants exhibited moderately elevated levels of melanin and capsule production relative to the wild type. Epistasis experiments indicate that Pde1 functions downstream of the Galpha subunit Gpa1, which initiates cAMP-dependent signaling in response to an extracellular signal. Previous work has shown that the PKA catalytic subunit Pka1 governs cAMP levels via a negative feedback loop. Here we show that a pde1Delta pka1Delta mutant strain exhibits cAMP levels that are dramatically increased ( approximately 15-fold) relative to those in a pka1Delta single mutant strain and that a site-directed mutation in a consensus PKA phosphorylation site reduces Pde1 function. These data provide evidence that fluctuations in cAMP levels are modulated by both Pka1-dependent regulation of Pde1 and another target that comprise a robust negative feedback loop to tightly constrain intracellular cAMP levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.