Evidence map›Paper›PMID 26507661›Full record

ArticleThe Journal of biological chemistry2015

Cyclic Nucleotide-dependent Protein Kinases Target ARHGAP17 and ARHGEF6 Complexes in Platelets.

Zoltan Nagy, Kieran Wynne, Alexander von Kriegsheim, Stepan Gambaryan, Albert Smolenski

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. 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
1.7field-weighted citation impact, top 16% 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, 34 citations in OpenAlex.

  1. Review
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  11. Proteomics: A Tool to Study Platelet Function.International journal of molecular sciences · 2021
    Review
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  18. RXR Ligands Negatively Regulate Thrombosis and Hemostasis.Arteriosclerosis, thrombosis, and vascular biology · 2017
    Article
  19. Review
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

5 authors at 2 institutions in 2 countries.

Zoltan NagyFrom the UCD Conway Institute and the School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Kieran WynneMass Spectrometry Resource, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Alexander von KriegsheimSystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland, and.
Stepan GambaryanSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Prospect, St. Petersburg, 194223 Russia.
Albert SmolenskiFrom the UCD Conway Institute and the School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland, albert.smolenski@ucd.ie.
University College Dublin · IEInstitute of Evolutionary Physiology and Biochemistry · RU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Endothelial cells release prostacyclin (PGI2) and nitric oxide (NO) to inhibit platelet functions. PGI2 and NO effects are mediated by cyclic nucleotides, cAMP- and cGMP-dependent protein kinases (PKA, PKG), and largely unknown PKA and PKG substrate proteins. The small G-protein Rac1 plays a key role in platelets and was suggested to be a target of cyclic nucleotide signaling. We confirm that PKA and PKG activation reduces Rac1-GTP levels. Screening for potential mediators of this effect resulted in the identification of the Rac1-specific GTPase-activating protein ARHGAP17 and the guanine nucleotide exchange factor ARHGEF6 as new PKA and PKG substrates in platelets. We mapped the PKA/PKG phosphorylation sites to serine 702 on ARHGAP17 using Phos-tag gels and to serine 684 on ARHGEF6. We show that ARHGAP17 binds to the actin-regulating CIP4 protein in platelets and that Ser-702 phosphorylation interferes with this interaction. Reduced CIP4 binding results in enhanced inhibition of cell migration by ARHGAP17. Furthermore, we show that ARHGEF6 is constitutively linked to GIT1, a GAP of Arf family small G proteins, and that ARHGEF6 phosphorylation enables binding of the 14-3-3 adaptor protein to the ARHGEF6/GIT1 complex. PKA and PKG induced rearrangement of ARHGAP17- and ARHGEF6-associated protein complexes might contribute to Rac1 regulation and platelet inhibition.

Indexed as

Blood PlateletsCyclic AMP-Dependent Protein KinasesCyclic GMP-Dependent Protein KinasesGTPase-Activating ProteinsHEK293 CellsHeLa CellsHumansPhosphorylationRho Guanine Nucleotide Exchange FactorsSubstrate SpecificityARHGAP17 protein, humanARHGEF6 protein, humanCyclic AMP-Dependent Protein KinasesCyclic GMP-Dependent Protein KinasesGTPase-Activating ProteinsRho Guanine Nucleotide Exchange Factorscyclic AMP (cAMP)cyclic GMP (cGMP)phosphorylationplateletRac (Rac GTPase)

Identifiers

PMID26507661
PMCPMC4705978
OpenAlexW2165308017

What OpenQuestion holds

Textmetadata
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.