Evidence map›Paper›PMID 34810254›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Click chemistry-enabled CRISPR screening reveals GSK3 as a regulator of PLD signaling.

Timothy W Bumpus, Shiying Huang, Reika Tei, Jeremy M Baskin

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Synthetic Lipid Biology.Chemical reviews · 2025
    Review
  5. Optogenetic Strategies for Optimizing the Performance of Phospholipids Biosensors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  6. Review
  7. Article
  8. Chemical Tools for Lipid Cell Biology.Accounts of chemical research · 2023
    Article
  9. Click chemistry and drug delivery: A bird's-eye view.Acta pharmaceutica Sinica. B · 2023
    Review
  10. Adding a Chemical Biology Twist to CRISPR Screening.Israel journal of chemistry · 2023
    Article
  11. Imaging and Editing the Phospholipidome.Accounts of chemical research · 2022
    Review
  12. Review
  13. 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

4 authors at 1 institution in 1 country.

Timothy W BumpusDepartment of Chemistry and Chemical Biology and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853.ORCID 0000-0001-5866-5361
Shiying HuangDepartment of Chemistry and Chemical Biology and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853.
Reika TeiDepartment of Chemistry and Chemical Biology and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853.ORCID 0000-0002-9492-9309
Jeremy M BaskinDepartment of Chemistry and Chemical Biology and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853 jeremy.baskin@cornell.edu.ORCID 0000-0003-2939-3138
Cornell University · US

Funding

Training future leaders at the chemistry-biology interfaceT32GM138826 · NIGMS · CORNELL UNIVERSITY · PI Jeremy Baskin · 2021 to 2026
$2.6M
NIGMS NIH HHS T32 GM138826
6 · The paper itself

Abstract

Enzymes that produce second messengers are highly regulated. Revealing the mechanisms underlying such regulation is critical to understanding both how cells achieve specific signaling outcomes and return to homeostasis following a particular stimulus. Pooled genome-wide CRISPR screens are powerful unbiased approaches to elucidate regulatory networks, their principal limitation being the choice of phenotype selection. Here, we merge advances in bioorthogonal fluorescent labeling and CRISPR screening technologies to discover regulators of phospholipase D (PLD) signaling, which generates the potent lipid second messenger phosphatidic acid. Our results reveal glycogen synthase kinase 3 as a positive regulator of protein kinase C and PLD signaling. More generally, this work demonstrates how bioorthogonal, activity-based fluorescent tagging can expand the power of CRISPR screening to uncover mechanisms regulating specific enzyme-driven signaling pathways in mammalian cells.

Indexed as

Biological PhenomenaClick ChemistryClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGlycogen Synthase Kinase 3HEK293 CellsHumansK562 CellsPhosphatidic AcidsPhospholipase DProtein Kinase C-alphaSecond Messenger SystemsSignal TransductionGlycogen Synthase Kinase 3Phosphatidic AcidsPhospholipase Dphospholipase D1Protein Kinase C-alphaclick chemistryCRISPRiCRISPR screeningGSK3phospholipase D

Identifiers

PMID34810254
PMCPMC8640934
OpenAlexW3217253007

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.