ArticleThe Journal of biological chemistry2008
Isolation of intrinsically active (MEK-independent) variants of the ERK family of mitogen-activated protein (MAP) kinases.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 62 citations in OpenAlex.
- ERK autoinhibition mechanism informs a drug combination strategy.Protein science : a publication of the Protein Society · 2026Article
- Conformation-Specific Design: Engineering Extracellular Signal-Regulated Kinase 2 Variants with Bias toward Active or Inactive States.ACS omega · 2026Article
- Erk1Oncogene · 2025Article
- ERK1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility.Molecular oncology · 2025Article
- ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.NPJ precision oncology · 2024Review
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2.International journal of molecular sciences · 2023Review
- Differential Modulation of the Phosphoproteome by the MAP Kinases Isoforms p38α and p38β.International journal of molecular sciences · 2023Article
- Condensed-phase signaling can expand kinase specificity and respond to macromolecular crowding.Molecular cell · 2022Article
- Development of small molecule extracellular signal-regulated kinases (ERKs) inhibitors for cancer therapy.Acta pharmaceutica Sinica. B · 2022Review
- TRIM15 and CYLD regulate ERK activation via lysine-63-linked polyubiquitination.Nature cell biology · 2021Article
- Active p38α causes macrovesicular fatty liver in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Review
- Article
- Article
- Overexpression of Tpl2 is linked to imatinib resistance and activation of MEK-ERK and NF-κB pathways in a model of chronic myeloid leukemia.Molecular oncology · 2018Article
- Phenotypic Characterization of a Comprehensive Set of MAPK1/ERK2 Missense Mutants.Cell reports · 2016Article
- Variants of the yeast MAPK Mpk1 are fully functional independently of activation loop phosphorylation.Molecular biology of the cell · 2016Article
- Signaling pathways and posttranslational modifications of tau in Alzheimer's disease: the humanization of yeast cells.Microbial cell (Graz, Austria) · 2016Review
- Intrinsically active variants of Erk oncogenically transform cells and disclose unexpected autophosphorylation capability that is independent of TEY phosphorylation.Molecular biology of the cell · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MAPKs are key components of cell signaling pathways with a unique activation mechanism: i.e. dual phosphorylation of neighboring threonine and tyrosine residues. The ERK enzymes form a subfamily of MAPKs involved in proliferation, differentiation, development, learning, and memory. The exact role of each Erk molecule in these processes is not clear. An efficient strategy for addressing this question is to activate individually each molecule, for example, by expressing intrinsically active variants of them. However, such molecules were not produced so far. Here, we report on the isolation, via a specifically designed genetic screen, of six variants (each carries a point mutation) of the yeast MAPK Mpk1/Erk that are active, independent of upstream phosphorylation. One of the activating mutations, R68S, occurred in a residue conserved in the mammalian Erk1 (Arg-84) and Erk2 (Arg-65) and in the Drosophila ERK Rolled (Arg-80). Replacing this conserved Arg with Ser rendered these MAPKs intrinsically active to very high levels when tested in vitro as recombinant proteins. Combination of the Arg to Ser mutation with the sevenmaker mutation (producing Erk2(R65S+D319N) and Rolled(R80S+D334N)) resulted in even higher activity (45 and 70%, respectively, in reference to fully active dually phosphorylated Erk2 or Rolled). Erk2(R65S) and Erk2(R65S+D319N) were found to be spontaneously active also when expressed in human HEK293 cells. We further revealed the mechanism of action of the mutants and show that it involves acquisition of autophosphorylation activity. Thus, a first generation of Erk molecules that are spontaneously active in vitro and in vivo has been obtained.
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.