Evidence map›Paper›PMID 31958057›Full record

ArticleeLife2020

Membrane interactions of the globular domain and the hypervariable region of KRAS4b define its unique diffusion behavior.

Debanjan Goswami, De Chen, Yue Yang, Prabhakar R Gudla, John Columbus, Karen Worthy, Megan Rigby, Madeline Wheeler, Suman Mukhopadhyay, Katie Powell and 8 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

23 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. FLIM-FRET Protein-Protein Interaction Assay.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Machine learning-driven multiscale modeling reveals lipid-dependent dynamics of RAS signaling proteins.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  16. The role of KRAS splice variants in cancer biology.Frontiers in cell and developmental biology · 2022
    Review
  17. Review
  18. Article
  19. Article
  20. 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

18 authors at 3 institutions in 1 country.

Debanjan Goswami *NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.ORCID 0000-0001-5910-3811
De Chen *NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Yue YangBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, United States.
Prabhakar R GudlaNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
John ColumbusNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Karen WorthyNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Megan RigbyNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Madeline WheelerNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Suman MukhopadhyayNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Katie PowellNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
William BurganNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Vanessa WallNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Dominic EspositoNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Dhirendra K SimanshuNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Felice C LightstoneBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, United States.ORCID 0000-0003-1465-426X
Dwight V NissleyNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.
Frank McCormickUCSF Helen Diller Family Comprehensive Cancer Center, School of Medicine, University of California, San Francisco, San Francisco, United States.
Thomas TurbyvilleNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.ORCID 0000-0003-2638-9520
Frederick National Laboratory for Cancer Research · USLawrence Livermore National Laboratory · USUniversity of California, San Francisco · US

Funding

CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENCI NIH HHS NIH Contract HHSN261200800001EU.S. Department of Energy Joint Design of Advanced Computing Solutions for Cancer (JDACS4C)U.S. Department of Energy Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-JRNL-771099-DRAFT
6 · The paper itself

Abstract

The RAS proteins are GTP-dependent switches that regulate signaling pathways and are frequently mutated in cancer. RAS proteins concentrate in the plasma membrane via lipid-tethers and hypervariable region side-chain interactions in distinct nano-domains. However, little is known about RAS membrane dynamics and the details of RAS activation of downstream signaling. Here, we characterize RAS in live human and mouse cells using single-molecule-tracking methods and estimate RAS mobility parameters. KRAS4b exhibits confined mobility with three diffusive states distinct from the other RAS isoforms (KRAS4a, NRAS, and HRAS); and although most of the amino acid differences between RAS isoforms lie within the hypervariable region, the additional confinement of KRAS4b is largely determined by the protein's globular domain. To understand the altered mobility of an oncogenic KRAS4b, we used complementary experimental and molecular dynamics simulation approaches to reveal a detailed mechanism.

Indexed as

Cell MembraneProto-Oncogene Proteins p21(ras)AnimalsCell LineHeLa CellsHumansMiceMolecular Dynamics SimulationProtein DomainsProtein IsoformsKRAS4B protein, mouseKRAS protein, humanProtein IsoformsProto-Oncogene Proteins p21(ras)atomistic simulationcancercancer biologyhumanmousephysics of living systemsRAS diffusionsingle molecule tracking

Identifiers

PMID31958057
PMCPMC7060043
OpenAlexW2998848508

What OpenQuestion holds

Textmetadata
LicenceCC0
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.