Evidence map›Paper›PMID 36356576›Full record

ArticleCell systems2022

Systematic analysis of the MAPK signaling network reveals MAP3K-driven control of cell fate.

Amy F Peterson, Kayla Ingram, E J Huang, Jeeun Parksong, Connor McKenney, Gabriel S Bever, Sergi Regot

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.3field-weighted citation impact, top 6% 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

44 citing papers in PubMed, 44 citations in OpenAlex.

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  17. Molecular Mechanisms of Mangiferin on Neuroinflammation for Treating Major Depressive Disorder Based on Network Pharmacology and Bioinformatics Analysis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Amy F PetersonDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Biochemistry, Cellular, and Molecular Biology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kayla IngramDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Biochemistry, Cellular, and Molecular Biology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
E J HuangCenter for Functional Anatomy & Evolution, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jeeun ParksongDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Biochemistry, Cellular, and Molecular Biology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Connor McKenneyDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Biochemistry, Cellular, and Molecular Biology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Gabriel S BeverCenter for Functional Anatomy & Evolution, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sergi RegotDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Biochemistry, Cellular, and Molecular Biology Graduate Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: sregot@jhmi.edu.
Johns Hopkins University · US

Funding

Single Cell Analysis of MAPK Signaling Dynamics in MulticellularityR35GM133499 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Sergi Regot · 2019 to 2026
$3.3M
NIGMS NIH HHS R35 GM133499
6 · The paper itself

Abstract

The classic network of mitogen-activated protein kinases (MAPKs) is highly interconnected and controls a diverse array of biological processes. In multicellular eukaryotes, the MAPKs ERK, JNK, and p38 control opposing cell behaviors but are often activated simultaneously, raising questions about how input-output specificity is achieved. Here, we use multiplexed MAPK activity biosensors to investigate how cell fate control emerges from the connectivity and dynamics of the MAPK network. Through chemical and genetic perturbation, we systematically explore the outputs and functions of all the MAP3 kinases encoded in the human genome and show that MAP3Ks control cell fate by triggering unique combinations of MAPK activity. We show that these MAPK activity combinations explain the paradoxical dual role of JNK signaling as pro-apoptotic or pro-proliferative kinase. Overall, our integrative analysis indicates that the MAPK network operates as a unit to control cell fate and shifts the focus from MAPKs to MAP3Ks to better understand signaling-mediated control of cell fate.

Indexed as

JNK Mitogen-Activated Protein KinasesMAP Kinase Signaling SystemHumansMitogen-Activated Protein KinasesPhosphorylationSignal TransductionJNK Mitogen-Activated Protein KinasesMitogen-Activated Protein KinasesMAP kinase networksingle-cell signaling dynamics

Identifiers

PMID36356576
PMCPMC9923805
OpenAlexW4308612123

What OpenQuestion 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 OpenQuestion graph.