Evidence map›Paper›PMID 24469460›Full record

ArticleThe Journal of biological chemistry2014

Nitration of tyrosine 247 inhibits protein kinase G-1α activity by attenuating cyclic guanosine monophosphate binding.

Saurabh Aggarwal, Christine M Gross, Ruslan Rafikov, Sanjiv Kumar, Jeffrey R Fineman, Britta Ludewig, Danny Jonigk, Stephen M Black

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

20 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Endothelial PHD2 deficiency induces nitrative stressThe European respiratory journal · 2022
    Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. The arabidopsis cyclic nucleotide interactome.Cell communication and signaling : CCS · 2016
    Article
  17. Endothelial and Smooth Muscle Cell Interactions in the Pathobiology of Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2016
    Review
  18. Article
  19. Article
  20. Article
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

8 authors at 4 institutions in 2 countries.

Saurabh AggarwalFrom the Pulmonary Disease Program, Vascular Biology Center, Georgia Regents University, Augusta, Georgia 30912.
Christine M Gross
Ruslan Rafikov
Sanjiv Kumar
Jeffrey R Fineman
Britta Ludewig
Danny Jonigk
Stephen M Black
Georgia Regents Medical Center · USAugusta University · USMedizinische Hochschule Hannover · DEUniversity of California, San Francisco · US

Funding

Therapeutic Mechanisms of RhoA Inhibition In Acute Lung InjuryP01HL101902 · NHLBI · AUGUSTA UNIVERSITY · PI BLACK, STEPHEN M · 2011 to 2016
$11.2M
PERINATAL PULMONARY HYPERTENSION: DEVELOPMENT MEDIATORSR01HL061284 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FINEMAN, JEFFREY R · 1999 to 2016
$8.3M
PERINATAL REGULATION OF THE ENDOTHELIAL NOS GENER01HL060190 · NHLBI · UNIVERSITY OF MONTANA · PI Stephen M Black · 1998 to 2026
$7.1M
Research Training in Pediatric Critical Care MedicineT32HD049303 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JEFFREY R FINEMAN · 2006 to 2026
$3.1M
ROS in Pulmonary Hypertension: Role of ADMAR01HL067841 · NHLBI · UNIVERSITY OF MONTANA · PI BLACK, STEPHEN M · 2002 to 2011
$2.6M
Perinatal regulation of TGF-beta1 during vascular remodelingR01HL084739 · NHLBI · AUGUSTA UNIVERSITY · PI BLACK, STEPHEN M · 2007 to 2010
$1.5M
NHLBI NIH HHS HL0101902NHLBI NIH HHS HL061284NHLBI NIH HHS HL084739NHLBI NIH HHS HL60190NHLBI NIH HHS HL67841NHLBI NIH HHS P01 HL101902NHLBI NIH HHS R01 HL060190NHLBI NIH HHS R01 HL061284NHLBI NIH HHS R01 HL067841NHLBI NIH HHS R01 HL084739NICHD NIH HHS T32 HD049303
6 · The paper itself

Abstract

The cGMP-dependent protein kinase G-1α (PKG-1α) is a downstream mediator of nitric oxide and natriuretic peptide signaling. Alterations in this pathway play a key role in the pathogenesis and progression of vascular diseases associated with increased vascular tone and thickness, such as pulmonary hypertension. Previous studies have shown that tyrosine nitration attenuates PKG-1α activity. However, little is known about the mechanisms involved in this event. Utilizing mass spectrometry, we found that PKG-1α is susceptible to nitration at tyrosine 247 and 425. Tyrosine to phenylalanine mutants, Y247F- and Y425F-PKG-1α, were both less susceptible to nitration than WT PKG-1α, but only Y247F-PKG-1α exhibited preserved activity, suggesting that the nitration of Tyr(247) is critical in attenuating PKG-1α activity. The overexpression of WT- or Y247F-PKG-1α decreased the proliferation of pulmonary artery smooth muscle cells (SMC), increased the expression of SMC contractile markers, and decreased the expression of proliferative markers. Nitrosative stress induced a switch from a contractile to a synthetic phenotype in cells expressing WT- but not Y247F-PKG-1α. An antibody generated against 3-NT-Y247 identified increased levels of nitrated PKG-1α in humans with pulmonary hypertension. Finally, to gain a more mechanistic understanding of how nitration attenuates PKG activity, we developed a homology model of PKG-1α. This model predicted that the nitration of Tyr(247) would decrease the affinity of PKG-1α for cGMP, which we confirmed using a [(3)H]cGMP binding assay. Our study shows that the nitration of Tyr(247) and the attenuation of cGMP binding is an important mechanism regulating in PKG-1α activity and SMC proliferation/differentiation.

Indexed as

AdultAnimalsAortaCardiovascular DiseasesCatalytic DomainCell DifferentiationCell ProliferationCells, CulturedCyclic GMPCyclic GMP-Dependent Protein Kinase Type IFemaleHEK293 CellsHumansMaleMass SpectrometryMiddle AgedCyclic GMPCyclic GMP-Dependent Protein Kinase Type INitrogenPeroxynitrous AcidTyrosineCyclic GMP (cGMP)Enzyme CatalysisMass Spectrometry (MS)Molecular ModelingPeroxynitriteProtein Kinase G (PKG)

Identifiers

PMID24469460
PMCPMC3953305
OpenAlexW1996902548

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.