Human Ser/Thr phosphatase regulatory subunits interactome
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap Velos
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cell Culture
SUBMITTER: 
Subbareddy Maddika
LAB HEAD: Dr. Maddika Subba Reddy
PROVIDER: PXD014772 | Pride | 2019-08-16
REPOSITORIES: Pride
Similar Datasets
Project description:Different transcriptome, metabolome, and phosphoproteome studies have already indicated a regulatory role of Ser/Thr phosphorylation in the central metabolism of S. aureus. However, it remains still unknown how this exactly tunes its metabolism. For that reason, Extreme Pathway Analysis was used to understand metabolic flux regulation by Ser/Thr phosphorylation. YANAsquare software and YANAvergence routine were chosen to calculate pathway activities of WT, ΔpknB, Δstp, and double mutant S. aureus NewmanHG strains. Gene expression data of S. aureus NewmanHG were collected taking the wild type and mutations of kinase (pknB), phosphatase (stp) or both (pknB/stp) phenotypes. The resulting flux changes were modelled with YANAvergence taking the different gene expression data and an established genome scale model of S. aureus metabolic modes as basis. The fluxes of the different strains were next calculated, taking the gene expression data into account. A concerted metabolic change of fluxes was observed. In particular the pathways for peptidoglycan, nucleotide, and aromatic amino acid synthesis as well as catabolism involving aspartate transaminase (GOT) changed significantly compared to the wild type. Single mutations of pknB and stp were compared to illustrate their different contribution to the phenotype, e.g. pyrimidine synthesis is dramatically impaired by pknB deletion but much less by loss of stp. In the double knock out strain, there is higher activity of peptidoglycan, purine, and aromatic amino acids synthesis from glucose, but lower activity of pyrimidine synthesis from glucose compared to WT. The results suggest a probable regulatory role of Ser/Thr phosphorylation in amino acid catabolism and the glycolysis/gluconeogenesis switch to provide the cell with sufficient cell wall components, nucleotides, and aromatic amino acids. Yvck is suggested to serve as regulatory protein linking Ser/Thr phosphorylation to the previous results of S. aureus metabolism. Moreover, Yvck seems in particular to be involved in the switch between glycolysis and gluconeogenesis. However, further studies based on experimental approaches are needed to demonstrate that Ser/Thr phosphorylation and Yvck are necessary for a correct cell growth under gluconeogenic conditions. The metabolic model allows not only a comprehensive representation of these changes for all involved pathways in the four strains, it further points out the function of the previously unannotated ycvk operon.. The relevance of these specific metabolic pathway adaptations regarding the pathogenicity of S.aureus and their contributions to the infection process will be analyzed and discussed.
2019-11-11 | GSE122362 | GEO
Project description:Sinorhizobium meliloti, a facultative microsymbiont of alfalfa, should fine-tune its cellular processes to live saprophytically in soils characterized with limited nutrients and diverse stresses. In this study, TiO2 enrichment and LC-MS/MS were used to uncover the site-specific Ser/Thr/Tyr phosphoproteome of S. meliloti in minimum medium at stationary phase. There are a total of 96 unique phosphorylated sites, with a Ser/Thr/Tyr distribution of 65:32:5, in 78 proteins. Phosphoproteins identified in S. meliloti showed a wide distribution pattern regarding to functional categories, such as replication, transcription, translation, posttranslational modification, transport and metabolism of amino acids, carbohydrate, inorganic ion, succinoglycan etc. Ser/Thr/Tyr phosphosites identified within the conserved motif in proteins of key cellular function indicate a crucial role of phosphorylation in modulating cellular physiology. Moreover, phosphorylation events potentially involved in rhizobial adaptation to diverse stresses were also discussed, such as those identified in SMa0114 and PhaP2 (polyhydroxybutyrate synthesis), ActR (pH stress and microaerobic adaption), SupA (potassium stress), chaperonin GroEL2 (viability and potentially symbiosis), and ExoP (succinoglycan synthesis and secretion). These Ser/Thr/Tyr phosphosites identified herein would be helpful for our further investigation and understanding of the role of phosphorylation in rhizobial physiology.
2015-10-05 | PXD002064 | Pride
Project description:Huarat2016 -Starvation-induced Ser/Thr
protein kinase ArnS (Saci_1181) (Model 14)
This model is described in the article:
ArnS, a kinase involved in
starvation-induced archaellum expression.
Haurat MF, Figueiredo AS, Hoffmann
L, Li L, Herr K, J Wilson A, Beeby M, Schaber J, Albers SV.
Mol. Microbiol. 2016 Oct; :
Abstract:
Organisms have evolved motility organelles that allow them
to move to favourable habitats. Cells integrate environmental
stimuli into intracellular signals to motility machineries to
direct this migration. Many motility organelles are complex
surface appendages that have evolved a tight, hierarchical
regulation of expression. In the crenearchaeon Sulfolobus
acidocaldarius, biosynthesis of the archaellum is regulated by
regulatory network proteins that control expression of
archaellum components in a phosphorylation-dependent manner. A
major trigger for archaellum expression is nutrient starvation,
but although some components are known, the regulatory cascade
triggered by starvation is poorly understood. In this work, the
starvation-induced Ser/Thr protein kinase ArnS (Saci_1181)
which is located proximally to the archaellum operon was
identified. Deletion of arnS results in reduced motility,
though the archaellum is properly assembled. Therefore, our
experimental and modelling results indicate that ArnS plays an
essential role in the precisely controlled expression of
archaellum components during starvation-induced motility in
Sulfolobus acidocaldarius. Furthermore they combined in vivo
experiments and mathematical models to describe for the first
time in archaea the dynamics of key regulators of archaellum
expression.
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2016-12-05 | MODEL1607210000 | BioModels
Project description:Protein Ser/Thr kinases are post-translational regulators of key molecular processes in bacteria, such as cell division and antibiotic tolerance. Here we characterize the E. coli toxin YjjJ (HipH), a putative protein kinase annotated as a member of the family of HipA-like Ser/Thr kinases which are involved in antibiotic tolerance. Using SILAC-based phosphoproteomics we provide experimental evidence that YjjJ is a Ser/Thr protein kinase and its primary protein substrates are the ribosomal protein RpmE (L31) and the carbon storage regulator CsrA. YjjJ activity impacts ribosome assembly, cell division and central carbon metabolism but it does not increase antibiotic tolerance as does its homologue HipA. Intriguingly, overproduction of YjjJ and its kinase-deficient variant can activate HipA and other kinases, pointing to a crosstalk between Ser/Thr kinases in E. coli.
2022-11-28 | PXD033071 | Pride
Project description:Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium in the environment and a leading cause of nosocomial infections worldwide. Therefore, it is listed by the World Health Organization as one of the human pathogens that urgently need to develop new antibacterial drugs. Recent findings have demonstrated that eukaryote-type Ser/Thr protein kinases play a vital role in regulating various bacterial physiological processes by catalyzing protein phosphorylation. Stk1 has been proved to be a Ser/Thr protein kinase in P. aeruginosa. However, the regulatory roles of Stk1 have not yet been revealed. Thus, we constructed the stk1 knockout mutant (∆stk1) from the P. aeruginosa PAO1 strain and employed a TMT labeling-based quantitative proteomic strategy to characterize proteome-wide changes in response to stk1 knockout. In total, 620 differentially expressed proteins, among which 288 proteins were upregulated and 332 proteins were downregulated, were identified in the ∆stk1 compared with the P. aeruginosa PAO1. Detailed bioinformatics analysis of these differentially expressed proteins were performed, including GO annotation, protein domain profile, the KEGG pathway, subcellular localization as well as enrichment analysis. Notably, downregulation of type Ⅳ pilus-related proteins and upregulation of T6SS-H1-related proteins were found in ∆stk1 strain, and the results were corroborated by quantitative PCR at the mRNA level. Further experiments confirmed that the loss of stk1 weakens the bacterial twitching motility and promotes a growth competition advantage, which is mediated by type Ⅳ pilus related proteins and T6SS-H1 related proteins, respectively. These findings contribute to a better understand the physiological role of Stk1, and the proteomic data will help further investigations of the roles and mechanisms of Stk1 in P. aeruginosa, though the detailed regulation and mechanism of Stk1 need to be further revealed.
2021-07-07 | PXD027148 | Pride
Project description:Regulatory protein phosphorylation controls nearly every normal and pathophysiological signaling system in eukaryotic cells. Despite great advances in mass spectrometry based-proteomics, the total number, localization and site-specific stoichiometry of this post-translational modification (PTM) are unknown. Here we develop stringent experimental and computational workflow, capable of mapping more than 50,000 distinct phosphorylated peptides in a single human cancer cell line. Label-free quantitation determined very high stoichiometries in mitosis or growth factor signaling and more than three-quarters of cellular proteins were detected as phosphoproteins. The proportion of phospho-Tyr drastically decreases as coverage of the phosphoproteome increases, whereas Ser/Thr sites only saturate for technical reasons. Tyrosine phosphorylation is maintained at especially low stoichiometric levels in the absence of specific signaling events. Unexpectedly, it is statistically enriched on higher abundance proteins and this correlates with the substrate Km values of tyrosine kinases. Our data suggests that P-Tyr should be considered a functionally separate PTM of eukaryotic proteomes.
2014-08-06 | PXD000612 | Pride
Project description:We report the mRNA expression profile of Streptococcus pneumoniae Type 2 D39 strain-derived mutant lacking the phpP gene encoding eukaryote-type ser/thr phosphatase and the stkP gene encoding Ser/Thr protein kinase.
2019-04-13 | GSE113337 | GEO
Project description:Regulatory protein phosphorylation controls nearly every normal and pathophysiological signaling system in eukaryotic cells. Despite great advances in mass spectrometry based-proteomics, the total number, localization and site-specific stoichiometry of this post-translational modification (PTM) are unknown. Here we develop stringent experimental and computational workflow, capable of mapping more than 50,000 distinct phosphorylated peptides in a single human cancer cell line. Label-free quantitation determined very high stoichiometries in mitosis or growth factor signaling and more than three-quarters of cellular proteins were detected as phosphoproteins. The proportion of phospho-Tyr drastically decreases as coverage of the phosphoproteome increases, whereas Ser/Thr sites only saturate for technical reasons. Tyrosine phosphorylation is maintained at especially low stoichiometric levels in the absence of specific signaling events. Unexpectedly, it is statistically enriched on higher abundance proteins and this correlates with the substrate Km values of tyrosine kinases. Our data suggests that P-Tyr should be considered a functionally separate PTM of eukaryotic proteomes.
2017-03-28 | MSV000080701 | MassIVE
Project description:Systems biology of S.aureus adaptation under Ser/Thr kinase wild type and mutations of kinase (pknB) or phosphatase (stp)
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