Evidence map›Paper›PMID 35202574›Full record

ArticleMolecular cell2022

Regulation of GTPase function by autophosphorylation.

Christian W Johnson, Hyuk-Soo Seo, Elizabeth M Terrell, Moon-Hee Yang, Fenneke KleinJan, Teklab Gebregiworgis, Genevieve M C Gasmi-Seabrook, Ezekiel A Geffken, Jimit Lakhani, Kijun Song and 10 more

Open access · greenAbstract read
In one paragraph

Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.6field-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

8 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Mechanism-Based Redesign of GAP to Activate Oncogenic Ras.Journal of the American Chemical Society · 2023
    Article
  5. Multiplexed imaging for probing RAS-RAF interactions in living cells.Biochimica et biophysica acta. Biomembranes · 2023
    Article
  6. Review
  7. Review
  8. 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

20 authors at 6 institutions in 2 countries.

Christian W JohnsonDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Hyuk-Soo SeoDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Elizabeth M TerrellLaboratory of Cell and Developmental Signaling, NCI-Frederick, Frederick, MD 21702, USA.
Moon-Hee YangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Fenneke KleinJanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Teklab GebregiworgisPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Genevieve M C Gasmi-SeabrookPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Ezekiel A GeffkenDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jimit LakhaniDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Kijun SongDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Puspalata BashyalDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Olesja PopowDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Andrea LiuDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Carla MattosDepartment of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
Christopher B MarshallPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Mitsuhiko IkuraPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Deborah K MorrisonLaboratory of Cell and Developmental Signaling, NCI-Frederick, Frederick, MD 21702, USA.
Sirano Dhe-PaganonDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Kevin M HaigisDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: Kevin_Haigis@dfci.harvard.edu.
Dana-Farber Cancer Institute · USUniversity Health Network · CABrigham and Women's Hospital · USHarvard University · USFrederick National Laboratory for Cancer Research · USNortheastern University · US

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI STEVEN E EALICK · 2018 to 2026
$34.2M
Regulation of Ras-Dependent Signal Transduction PathwaysZIABC010329 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MORRISON, DEBORAH · 2009 to 2025
$16.1M
Mouse models of Kras-mutant colorectal cancerR01CA246653 · NCI · DANA-FARBER CANCER INST · PI HAIGIS, KEVIN · 2020 to 2024
$3.1M
Tissue-specific genetic interactions in cancerR01CA232372 · NCI · DANA-FARBER CANCER INST · PI HAIGIS, KEVIN · 2018 to 2022
$2.9M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Basic and Translational studies of Ras-mutant colorectal cancerR01CA178017 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI HAIGIS, KEVIN · 2014 to 2018
$1.8M
REGULATION OF RAS DEPENDENT SIGNAL TRANSDUCTION PATHWAYSZ01BC010329 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MORRISON, DEBORAH K · 2000 to 2008
$1.8M
Advancing Multiplexed Isobaric Tag-based Strategies for Proteome ProfilingR01GM132129 · NIGMS · HARVARD MEDICAL SCHOOL · PI PAULO, JOAO A · 2019 to 2023
$1.7M
Cancer Research UKIntramural NIH HHS Z01 BC010329Intramural NIH HHS ZIA BC010329NCI NIH HHS R01 CA178017NCI NIH HHS R01 CA232372NCI NIH HHS R01 CA246653NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM132129NIH HHS S10 OD021527
6 · The paper itself

Abstract

A unifying feature of the RAS superfamily is a conserved GTPase cycle by which these proteins transition between active and inactive states. We demonstrate that autophosphorylation of some GTPases is an intrinsic regulatory mechanism that reduces nucleotide hydrolysis and enhances nucleotide exchange, altering the on/off switch that forms the basis for their signaling functions. Using X-ray crystallography, nuclear magnetic resonance spectroscopy, binding assays, and molecular dynamics on autophosphorylated mutants of H-RAS and K-RAS, we show that phosphoryl transfer from GTP requires dynamic movement of the switch II region and that autophosphorylation promotes nucleotide exchange by opening the active site and extracting the stabilizing Mg

Indexed as

GTP PhosphohydrolasesSignal TransductionAnimalsCrystallography, X-RayGuanosine TriphosphateMammalsNucleotidesProteinsGTP PhosphohydrolasesGuanosine TriphosphateNucleotidesProteinsautophosphorylationGTPasekinasemolecular dynamicsNMRphosphoryl transferprotein crystallographyRAFRASRASSF

Identifiers

PMID35202574
PMCPMC8986090
OpenAlexW4212931835

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.