Evidence map›Paper›PMID 32640021›Full record

ArticleBlood2020

Phosphoproteomic quantitation and causal analysis reveal pathways in GPVI/ITAM-mediated platelet activation programs.

Özgün Babur, Alexander R Melrose, Jennifer M Cunliffe, John Klimek, Jiaqing Pang, Anna-Liisa I Sepp, Jevgenia Zilberman-Rudenko, Samuel Tassi Yunga, Tony Zheng, Iván Parra-Izquierdo and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. Guideline
  2. Article
  3. Article
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  5. Article
  6. TRAF2 and NCK interacting kinase: a novel regulator of integrin αResearch and practice in thrombosis and haemostasis · 2025
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  9. ZO-2 seals the deal for platelet tight junctions.Research and practice in thrombosis and haemostasis · 2025
    Article
  10. Angiopoietin-like protein 2 inhibits thrombus formation.Molecular and cellular biochemistry · 2025
    Article
  11. Article
  12. Review
  13. Review
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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

17 authors at 3 institutions in 3 countries.

Özgün BaburDepartment of Molecular and Medical Genetics.
Alexander R MelroseKnight Cardiovascular Institute.
Jennifer M CunliffeProteomics Shared Resource.
John KlimekProteomics Shared Resource.
Jiaqing PangDepartment of Biomedical Engineering.
Anna-Liisa I SeppDepartment of Biomedical Engineering.
Jevgenia Zilberman-RudenkoDepartment of Biomedical Engineering.
Samuel Tassi YungaCancer Early Detection & Advanced Research Center.
Tony ZhengDepartment of Biomedical Engineering.
Iván Parra-IzquierdoKnight Cardiovascular Institute.
Jessica MinnierKnight Cancer Institute, and.
Owen J T McCartyDepartment of Biomedical Engineering.
Emek DemirDepartment of Molecular and Medical Genetics.
Ashok P ReddyProteomics Shared Resource.
Phillip A WilmarthProteomics Shared Resource.
Larry L DavidProteomics Shared Resource.
Joseph E AslanKnight Cardiovascular Institute.
Laboratory of Molecular Genetics · PLOregon Health & Science University · USCancer Institute (WIA) · IN

Funding

Understanding the origins of rapid recurrence of pancreatic cancer after resectionP30CA069533 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Grace B Gill · 1997 to 2026
$60.5M
Proteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Kate E Keller · 1995 to 2026
$19.4M
Characterization of Coagulation Factor-platelet Interactions: Role of FXIR01HL101972 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Owen J McCarty · 2010 to 2026
$8.5M
Pathway Maps of Platelet Phenotype and FunctionR01HL146549 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI ASLAN, JOSEPH E · 2019 to 2023
$2.5M
LTQ Orbitrap VelosS10OD012246 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI DAVID, LARRY L · 2012 to 2012
$854k
NCI NIH HHS P30 CA069533NEI NIH HHS P30 EY010572NHLBI NIH HHS R01 HL101972NHLBI NIH HHS R01 HL146549NIH HHS S10 OD012246
6 · The paper itself

Abstract

Platelets engage cues of pending vascular injury through coordinated adhesion, secretion, and aggregation responses. These rapid, progressive changes in platelet form and function are orchestrated downstream of specific receptors on the platelet surface and through intracellular signaling mechanisms that remain systematically undefined. This study brings together cell physiological and phosphoproteomics methods to profile signaling mechanisms downstream of the immunotyrosine activation motif (ITAM) platelet collagen receptor GPVI. Peptide tandem mass tag (TMT) labeling, sample multiplexing, synchronous precursor selection (SPS), and triple stage tandem mass spectrometry (MS3) detected >3000 significant (false discovery rate < 0.05) phosphorylation events on >1300 proteins over conditions initiating and progressing GPVI-mediated platelet activation. With literature-guided causal inference tools, >300 site-specific signaling relations were mapped from phosphoproteomics data among key and emerging GPVI effectors (ie, FcRγ, Syk, PLCγ2, PKCδ, DAPP1). Through signaling validation studies and functional screening, other less-characterized targets were also considered within the context of GPVI/ITAM pathways, including Ras/MAPK axis proteins (ie, KSR1, SOS1, STAT1, Hsp27). Highly regulated GPVI/ITAM targets out of context of curated knowledge were also illuminated, including a system of >40 Rab GTPases and associated regulatory proteins, where GPVI-mediated Rab7 S72 phosphorylation and endolysosomal maturation were blocked by TAK1 inhibition. In addition to serving as a model for generating and testing hypotheses from omics datasets, this study puts forth a means to identify hemostatic effectors, biomarkers, and therapeutic targets relevant to thrombosis, vascular inflammation, and other platelet-associated disease states.

Indexed as

AlgorithmsAnimalsHumansPlatelet ActivationPlatelet Membrane GlycoproteinsProteomicsSignal TransductionPlatelet Membrane Glycoproteinsplatelet membrane glycoprotein VI

Identifiers

PMID32640021
PMCPMC7702475
OpenAlexW3041517935

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.