Evidence map›Paper›PMID 37407549›Full record

ArticleNature communications2023

RAS-independent ERK activation by constitutively active KSR3 in non-chordate metazoa.

Aline Chessel, Noémie De Crozé, Maria Dolores Molina, Laura Taberner, Philippe Dru, Luc Martin, Thierry Lepage

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

7 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
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  4. A mechanosensitive circuit of FAK, ROCK, and ERK controls biomineral growth and morphology in the sea urchin embryo.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. 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

7 authors at 2 institutions in 2 countries.

Aline ChesselInstitut de Biologie Valrose CNRS, Université Côte d'Azur, Nice, France.
Noémie De CrozéInstitut de Biologie Valrose CNRS, Université Côte d'Azur, Nice, France.
Maria Dolores MolinaDepartment of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain.
Laura TabernerInstitut de Biologie Valrose CNRS, Université Côte d'Azur, Nice, France.ORCID 0000-0002-9296-3183
Philippe DruCNRS, Laboratoire de Biologie du Développement de Villefranche-sur-Mer (LBDV), Institut de la Mer de Villefranche, 181 Chemin du Lazaret, 06230, Villefranche-sur-Mer, France.ORCID 0000-0003-0008-0787
Luc MartinInstitut de Biologie Valrose CNRS, Université Côte d'Azur, Nice, France.
Thierry LepageInstitut de Biologie Valrose CNRS, Université Côte d'Azur, Nice, France. tlepage@unice.fr.ORCID 0000-0003-2889-5064
Centre National de la Recherche Scientifique · FRUniversitat de Barcelona · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

During early development of the sea urchin embryo, activation of ERK signalling in mesodermal precursors is not triggered by extracellular RTK ligands but by a cell-autonomous, RAS-independent mechanism that was not understood. We discovered that in these cells, ERK signalling is activated through the transcriptional activation of a gene encoding a protein related to Kinase Suppressor of Ras, that we named KSR3. KSR3 belongs to a family of catalytically inactive allosteric activators of RAF. Phylogenetic analysis revealed that genes encoding kinase defective KSR3 proteins are present in most non-chordate metazoa but have been lost in flies and nematodes. We show that the structure of KSR3 factors resembles that of several oncogenic human RAF mutants and that KSR3 from echinoderms, cnidarians and hemichordates activate ERK signalling independently of RAS when overexpressed in cultured cells. Finally, we used the sequence of KSR3 factors to identify activating mutations of human B-RAF. These findings reveal key functions for this family of factors as activators of RAF in RAS-independent ERK signalling in invertebrates. They have implications on the evolution of the ERK signalling pathway and suggest a mechanism for its co-option in the course of evolution.

Indexed as

MAP Kinase Signaling SystemSignal TransductionAnimalsHumansPhylogenyProtein KinasesProto-Oncogene Proteins c-rafProtein KinasesProto-Oncogene Proteins c-raf

Identifiers

PMID37407549
PMCPMC10322840
OpenAlexW4383223514

What OpenQuestion holds

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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.