ArticleMolecular biology of the cell2016
Intrinsically active variants of Erk oncogenically transform cells and disclose unexpected autophosphorylation capability that is independent of TEY phosphorylation.
Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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.
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.
Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Erk inhibitors intercept Erk-mediated negative feedback while imposing cell-cycle arrest and activating p38.iScience · 2026Article
- Conformation-Specific Design: Engineering Extracellular Signal-Regulated Kinase 2 Variants with Bias toward Active or Inactive States.ACS omega · 2026Article
- Identification of Novel Extracellular-Signal-Regulated Kinase 2 Inhibitors Through Machine Learning-Driven De Novo Design, Molecular Docking, and Free-Energy Perturbation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Erk1Oncogene · 2025Article
- ERK1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility.Molecular oncology · 2025Article
- Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer.Science (New York, N.Y.) · 2024Article
- Conformation selection by ATP-competitive inhibitors and allosteric communication in ERK2.eLife · 2024Article
- ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.NPJ precision oncology · 2024Review
- Review
- ERK2-topoisomerase II regulatory axis is important for gene activation in immediate early genes.Nature communications · 2023Article
- Conformation Selection by ATP-competitive Inhibitors and Allosteric Communication in ERK2.bioRxiv : the preprint server for biology · 2023Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Development of small molecule extracellular signal-regulated kinases (ERKs) inhibitors for cancer therapy.Acta pharmaceutica Sinica. B · 2022Review
- Copper dependent ERK1/2 phosphorylation is essential for the viability of neurons and not glia.Metallomics : integrated biometal science · 2022Article
- Review
- Sublytic C5b-9 induces glomerular mesangial cell proliferation via ERK1/2-dependent SOX9 phosphorylation and acetylation by enhancing Cyclin D1 in rat Thy-1 nephritis.Experimental & molecular medicine · 2021Article
- Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy.Cardiology journal · 2021Review
- The Dephosphorylation of p70S6 (ThrNeurotoxicity research · 2020Article
- Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
The receptor-tyrosine kinase (RTK)/Ras/Raf pathway is an essential cascade for mediating growth factor signaling. It is abnormally overactive in almost all human cancers. The downstream targets of the pathway are members of the extracellular regulated kinases (Erk1/2) family, suggesting that this family is a mediator of the oncogenic capability of the cascade. Although all oncogenic mutations in the pathway result in strong activation of Erks, activating mutations in Erks themselves were not reported in cancers. Here we used spontaneously active Erk variants to check whether Erk's activity per se is sufficient for oncogenic transformation. We show that Erk1(R84S) is an oncoprotein, as NIH3T3 cells that express it form foci in tissue culture plates, colonies in soft agar, and tumors in nude mice. We further show that Erk1(R84S) and Erk2(R65S) are intrinsically active due to an unusual autophosphorylation activity they acquire. They autophosphorylate the activatory TEY motif and also other residues, including the critical residue Thr-207 (in Erk1)/Thr-188 (in Erk2). Strikingly, Erk2(R65S) efficiently autophosphorylates its Thr-188 even when dually mutated in the TEY motif. Thus this study shows that Erk1 can be considered a proto-oncogene and that Erk molecules possess unusual autoregulatory properties, some of them independent of TEY phosphorylation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.