ArticleMolecular and cellular biology2008
Single and combined silencing of ERK1 and ERK2 reveals their positive contribution to growth signaling depending on their expression levels.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 201 citations in OpenAlex.
- ERK autoinhibition mechanism informs a drug combination strategy.Protein science : a publication of the Protein Society · 2026Article
- Article
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Review
- Discovery and optimization of a guanylhydrazone-based small molecule to replace bFGF for cell culture applications.Biochemistry and biophysics reports · 2025Article
- ERK1/2 Signaling in Intrahepatic Cholangiocarcinoma: From Preclinical Advances to Therapeutic Strategies.Biology · 2025Review
- Interdependency and differential expression of ERK1 and ERK2 in breast and melanoma cell lines.Journal of the Egyptian National Cancer Institute · 2024Article
- Tonic ErbB signaling underlies TGFβ-induced activation of ERK and is required for lens cell epithelial to myofibroblast transition.Molecular biology of the cell · 2024Article
- Extracellular Signal-Regulated Kinases Play Essential but Contrasting Roles in Osteoclast Differentiation.International journal of molecular sciences · 2023Review
- N-terminal alanine-rich (NTAR) sequences drive precise start codon selection resulting in elevated translation of multiple proteins including ERK1/2.Nucleic acids research · 2023Article
- ERK1/2 inhibitors act as monovalent degraders inducing ubiquitylation and proteasome-dependent turnover of ERK2, but not ERK1.The Biochemical journal · 2023Article
- The Role of ERK1/2 Pathway in the Pathophysiology of Alzheimer's Disease: An Overview and Update on New Developments.Cellular and molecular neurobiology · 2023Review
- Article
- Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis.Science advances · 2022Article
- N-WASP Attenuates Cell Proliferation and Migration through ERK2-Dependent Enhanced Expression of TXNIP.Biology · 2022Article
- Article
- Article
- U0126: Not only a MAPK kinase inhibitor.Frontiers in pharmacology · 2022Review
- Identification of potential extracellular signal-regulated protein kinase 2 inhibitors based on multiple virtual screening strategies.Frontiers in pharmacology · 2022Article
- Contributions of extracellular-signal regulated kinase 1/2 activity to the memory trace.Frontiers in molecular neuroscience · 2022Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proteins ERK1 and ERK2 are highly similar, are ubiquitously expressed, and share activators and substrates; however, erk2 gene invalidation is lethal in mice, while erk1 inactivation is not. We ablated ERK1 and/or ERK2 by RNA interference and explored their relative roles in cell proliferation and immediate-early gene (IEG) expression. Reducing expression of either ERK1 or ERK2 lowered IEG induction by serum; however, silencing of only ERK2 slowed down cell proliferation. When both isoforms were silenced simultaneously, compensating activation of the residual pool of ERK1/2 masked a more deleterious effect on cell proliferation. It was only when ERK2 activation was clamped at a limiting level that we demonstrated the positive contribution of ERK1 to cell proliferation. We then established that ERK isoforms are activated indiscriminately and that their expression ratio correlated exactly with their activation ratio. Furthermore, we determined for the first time that ERK1 and ERK2 kinase activities are indistinguishable in vitro and that erk gene dosage is essential for survival of mice. We propose that the expression levels of ERK1 and ERK2 drive their apparent biological differences. Indeed, ERK1 is dispensable in some vertebrates, since it is absent from chicken and frog genomes despite being present in all mammals and fishes sequenced so far.
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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.