Evidence map›Paper›PMID 32085646›Full record

ArticleCells2020

The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human Platelets.

Elena J Kumm, Oliver Pagel, Stepan Gambaryan, Ulrich Walter, René P Zahedi, Albert Smolenski, Kerstin Jurk

Open access · goldAbstract read
In one paragraph

Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 26 citations in OpenAlex.

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  10. NovelCells · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 4 countries.

Elena J KummCenter for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Oliver PagelLeibniz-Institut für Analytische Wissenschaften - ISAS - e.V., 44227 Dortmund, Germany.
Stepan GambaryanCenter for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Ulrich WalterCenter for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
René P ZahediLeibniz-Institut für Analytische Wissenschaften - ISAS - e.V., 44227 Dortmund, Germany.
Albert SmolenskiUCD Conway Institute, UCD School of Medicine and Medical Science, University College Dublin, Dublin, D04 V1W8, Ireland.
Kerstin JurkCenter for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Johannes Gutenberg University Mainz · DEInstitute of Evolutionary Physiology and Biochemistry · RUJewish General Hospital · CALeibniz Institute for Analytical Sciences - ISAS · DEUniversity College Dublin · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The cell cycle is controlled by microtubule-associated serine/threonine kinase-like (MASTL), which phosphorylates the cAMP-regulated phosphoproteins 19 (ARPP19) at S62 and 19e/α-endosulfine (ENSA) at S67and converts them into protein phosphatase 2A (PP2A) inhibitors. Based on initial proteomic data, we hypothesized that the MASTL-ENSA/ARPP19-PP2A pathway, unknown until now in platelets, is regulated and functional in these anucleate cells. We detected ENSA, ARPP19 and various PP2A subunits (including seven different PP2A B-subunits) in proteomic studies of human platelets. ENSA-S109/ARPP19-S104 were efficiently phosphorylated in platelets treated with cAMP- (iloprost) and cGMP-elevating (NO donors/riociguat) agents. ENSA-S67/ARPP19-S62 phosphorylations increased following PP2A inhibition by okadaic acid (OA) in intact and lysed platelets indicating the presence of MASTL or a related protein kinase in human platelets. These data were validated with recombinant ENSA/ARPP19 and phospho-mutants using recombinant MASTL, protein kinase A and G. Both ARPP19 phosphorylation sites S62/S104 were dephosphorylated by platelet PP2A, but only S62-phosphorylated ARPP19 acted as PP2A inhibitor. Low-dose OA treatment of platelets caused PP2A inhibition, diminished thrombin-stimulated platelet aggregation and increased phosphorylation of distinct sites of VASP, Akt, p38 and ERK1/2 MAP kinases. In summary, our data establish the entire MASTL(like)-ENSA/ARPP19-PP2A pathway in human platelets and important interactions with the PKA, MAPK and PI3K/Akt systems.

Indexed as

Blood DonorsBlood PlateletsCell Cycle CheckpointsCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic GMPCyclic GMP-Dependent Protein KinasesHEK293 CellsHumansIntercellular Signaling Peptides and ProteinsMicrotubule-Associated ProteinsOkadaic AcidPhosphoproteinsPhosphorylationPlatelet AggregationProtein Phosphatase 2Cyclic AMPCyclic AMP-Dependent Protein Kinasescyclic AMP-regulated phosphoprotein 19Cyclic GMPCyclic GMP-Dependent Protein KinasesendosulfineIntercellular Signaling Peptides and ProteinsMASTL protein, humanMicrotubule-Associated ProteinsOkadaic AcidPhosphoproteinsProtein Phosphatase 2Protein Serine-Threonine KinasesARPP19cyclic AMPcyclic GMPENSAMAP kinaseplateletsserine/threonine protein phosphatases

Identifiers

PMID32085646
PMCPMC7072724
OpenAlexW3007921304

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.