Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Phosphodiesterase 1b (Pde1b) governs development and immune responses of myeloid and lymphoid cells through regulation of cyclic nucleotide-dependent protein kinases

ABSTRACT: Elevated cAMP and cGMP levels suppress immune functions in antigen presenting cells, while phosphodiesterases enzymatically degrade these cyclic nucleotides to regulate their intracellular concentrations. This study demonstrates that selective expression of the calcium/calmodulin-dependent phosphodiesterase 1b (Pde1b) in specific dendritic cell (DC) and macrophage subsets is essential for promoting inflammation and adaptive immunity. Utilizing single-cell RNA sequencing and multiparameter flow cytometry, Pde1b deficiency was found to alter gene expression and protein functions involved in development or immune effector activity in DC, macrophages, granulocytes, B cells, NK cells and memory T cells. In vivo pathogen challenge studies in Pde1b-deficient mice resulted in markedly attenuated pro-inflammatory and antigen-specific T cell responses. Notably, Pde1b-deficient DC and macrophages exhibited elevated cyclic nucleotides levels and enhanced cyclic nucleotide-dependent PKA and PKG activity. These findings establish Pde1b as a pivotal regulator of cyclic nucleotide signaling that shapes immune development and responses.

ORGANISM(S): Mus musculus

PROVIDER: GSE297611 | GEO | 2026/09/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Interaction of cGMP-dependent protein kinase and HAP1

Project description:Here, we use cAMP-based chemical proteomics approach, employing competitive concentrations of free cyclic nucleotides to isolate PKA and PKG and their secondary interactors.

2015-02-09 | PXD001434 | Pride

Phosphodiesterase 3A deficient in breast cancer cell

Project description:Analysis of MDA-MB-231 breast tumor cell from knocking-down phosphodiesterase 3A (PDE3A), a cyclic nucleotide phosphodiesterase. Results provide insight into the role of PDE3A in breast tumor progression and metastasis.

2019-09-21 | GSE130569 | GEO

Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery

Project description:Cyclic nucleotides are important signalling molecules across evolution, but their roles in malaria parasites are poorly understood. We have investigated the role of cAMP in asexual blood stage development of Plasmodium falciparum through conditional disruption of adenylyl cyclase (ACβ) and its downstream effector, cAMP-dependent protein kinase (PKA). We show that both production of cAMP and activity of PKA are critical for erythrocyte invasion, whilst key developmental steps that precede invasion still take place in the absence of cAMP-dependent signalling. We also show that another protein with putative cyclic nucleotide binding sites, PfEpac, does not play an essential role in cyclic nucleotide signalling in blood stages. We identify over 2,000 sites whose phosphorylation is dependent on cAMP signalling and we provide mechanistic insight as to how cAMP-dependent phosphorylation of the cytoplasmic domain of the essential invasion adhesin apical membrane antigen 1 (AMA1) controls erythrocyte invasion.

2019-05-14 | PXD012143 | Pride

Phosphodiesterase beta controls cAMP signalling during malaria parasite erythrocyte invasion

Project description:Cyclic nucleotide signalling is a major regulator of malaria parasite differentiation. Specific phosphodiesterase (PDE) enzymes are known to control cGMP levels in the parasite, but the mechanisms by with cAMP is regulated remain enigmatic. Here we show that P. falciparum PDEbeta translocates via the ER to an apical location and finally to the plasma membrane of merozoites within the segmented schizont. PDEbeta is essential for blood stage replication, with conditional gene disruption causing a profound invasion phenotype and rapid death of those merozoites that are able to invade a host erythrocyte. Importantly we also demonstrate that PDEbeta is able to hydrolyse both cAMP and cGMP. Loss of PDEbeta activity results in significantly elevated levels of cAMP which correlate temporally with the observed reduction in merozoite invasion. Quantitative phosphoproteomic analysis revealed a >2-fold increase in phosphorylation for >250 phosphosites following silencing of PfPDEbeta. These included a highly significant increase in phosphorylation at PKA substrate consensus sequences. Our results suggest that dysregulated phosphorylation of MyoA S19 and AMA1 S610 likely contributes to the PfPDEbeta knockout invasion phenotype, that PKG activity governs cAMP levels and PKA activation prior to merozoite egress, and that PfPDEbeta has an essential function in regulation cAMP levels in early intra-erythrocytic development in P. falciparum.

2019-02-27 | PXD009157 | Pride

Transcriptional profiling to elucidate processes regulated by 2',3'-cyclic nucleotide phosphodiesterase (CNPase) in Salmonella Typhimurium 14028s (Salmonella) II.

Project description:The impact of 2',3'-cyclic nucleotide phosphodiesterase (CNPase) on global gene expression in Salmonella was investigated by heterologous expression of mammalian CNPase in a strain containing a deletion of the 'rna' gene. 'rna' encodes an endoribonuclease capable of hydrolyzing RNA into 2',3'-cyclic nucleotide monophosphates (2',3'-cNMPs) such that deletion of 'rna' drastically reduces 2',3'-cNMPs presence to undetectable levels. Expression of CNPase in this strain allowed any effects of CNPase unrelated to 2',3'-cNMPs to be observed.

2021-11-09 | GSE184190 | GEO

Transcriptional profiling to elucidate processes regulated by 2',3'-cyclic nucleotide phosphodiesterase (CNPase) in Escherichia coli K12 BW25113 (E. coli)

Project description:The impact of 2',3'-cyclic nucleotide phosphodiesterase (CNPase) on global gene expression in E. coli was investigated by heterologous expression of mammalian CNPase in a strain containing a deletion of the 'rna' gene. 'rna' encodes an endoribonuclease capable of hydrolyzing RNA into 2',3'-cyclic nucleotide monophosphates (2',3'-cNMPs) such that deletion of 'rna' drastically reduces 2',3'-cNMPs levels to undetectable levels. Expression of CNPase in this strain allowed any effects of CNPase unrelated to 2',3'-cNMPs to be observed.

2021-11-09 | GSE182184 | GEO

Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites

Project description:The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals necessary for malaria parasite development

2024-06-24 | PXD048979 | Pride

Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites

2024-06-24 | PXD049017 | Pride

Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites

2024-06-24 | PXD049083 | Pride

A role for Multidrug Resistance Protein 4 (MRP4; ABCC4) in human Dendritic Cell migration.

Project description:The capacity of dendritic cells (DC) to migrate from peripheral organs to lymph nodes (LN) is an important event in the initiation of a T cell-mediated immune response. Previously it was shown that the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; ABCB1) and the 2 multidrug resistance protein 1 (MRP1; ABCC1) play a role in both human and murine DC migration. Here we show that a more recently discovered family-member, MRP4 (ABCC4) is expressed on both epidermal and dermal human skin DC and contributes to the migratory capacity of DC. Pharmacological inhibition of MRP4 activity or down-regulation through RNAi in DC resulted in reduced migration of DC from human skin explants and of in vitro generated Langerhans cells. The responsible MRP4 substrate remains to be identified as exogenous addition of MRP4’s known substrates PGE2, leukotriene B4 and D4 or cyclic nucleotides (all previously implicated in DC migration) could not restore migration. This notwithstanding, our data show that MRP4 is an important molecule, significantly contributing to human DC migration towards the draining lymph nodes, and thereby relevant for the initiation of an immune response and a possible target for immunotherapy. Keywords: cell type comparison, RNAi knockdown for MRP4 2 samples were analyzed to compare. Immature DC cultured from MUTZ3 (reference control) or from MUTZ3-shMRP4 cells

2008-07-12 | E-GEOD-12089 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data