ArticleNature medicine2009
A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy.
Article in Nature medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 225 citations in OpenAlex.
- ZBED6 deficiency drives pathological cardiac hypertrophy through MEOX1-ERK1/2-dependent autophagy dysfunction.PLoS genetics · 2026Article
- ERK-Mediated Phosphorylation of YAP Defines a Noncanonical FGF Signaling Mechanism in Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- GCN5-ERK lactylation-phosphorylation loop amplifies lactate-driven cancer progression.Nature chemical biology · 2026Article
- Molecular Frameworks for ERK1/2 Inhibition: Lessons from Synthetic and SAR Explorations.ACS omega · 2025Review
- Erk1Oncogene · 2025Article
- Proteomic surveys of the mouse heart unveil cardiovascular responses to nitric oxide/cGMP signaling deficiencies.Communications biology · 2025Article
- Using artificial intelligence and promoter-level transcriptome analysis to identify a biomarker as a possible prognostic predictor of cardiac complications in male patients with Fabry disease.Molecular genetics and metabolism reports · 2024Article
- Sulfenylation of ERK1/2: A novel mechanism for SOHeliyon · 2024Article
- Internalized β2-Adrenergic Receptors Oppose PLC-Dependent Hypertrophic Signaling.Circulation research · 2024Article
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice.Frontiers in endocrinology · 2024Article
- MEK inhibitors: a promising targeted therapy for cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction.Orphanet journal of rare diseases · 2023Article
- Review
- Phospholamban pentamerization increases sensitivity and dynamic range of cardiac relaxation.Cardiovascular research · 2023Article
- Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension-Mechanisms and Mitigation.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Central role for BRAF in cardiac hypertrophy: rethinking the pathological-physiological divide.Clinical science (London, England : 1979) · 2023Article
- Hippo pathway in intestinal diseases: focusing on ferroptosis.Frontiers in cell and developmental biology · 2023Review
- Alteration in tyrosine phosphorylation of cardiac proteome and EGFR pathway contribute to hypertrophic cardiomyopathy.Communications biology · 2022Article
- G protein-coupled receptor signaling: transducers and effectors.American journal of physiology. Cell physiology · 2022Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The extracellular-regulated kinases ERK1 and ERK2 (commonly referred to as ERK1/2) have a crucial role in cardiac hypertrophy. ERK1/2 is activated by mitogen-activated protein kinase kinase-1 (MEK1) and MEK2 (commonly referred to as MEK1/2)-dependent phosphorylation in the TEY motif of the activation loop, but how ERK1/2 is targeted toward specific substrates is not well understood. Here we show that autophosphorylation of ERK1/2 on Thr188 directs ERK1/2 to phosphorylate nuclear targets known to cause cardiac hypertrophy. Thr188 autophosphorylation requires the activation and assembly of the entire Raf-MEK-ERK kinase cascade, phosphorylation of the TEY motif, dimerization of ERK1/2 and binding to G protein betagamma subunits released from activated G(q). Thr188 phosphorylation of ERK1/2 was observed in isolated cardiomyocytes induced to undergo hypertrophic growth, in mice upon stimulation of G(q)-coupled receptors or after aortic banding and in failing human hearts. Experiments using transgenic mouse models carrying mutations at the Thr188 phosphorylation site of ERK2 suggested a causal relationship to cardiac hypertrophy. We propose that specific phosphorylation events on ERK1/2 integrate differing upstream signals (Raf1-MEK1/2 or G protein-coupled receptor-G(q)) to induce cardiac hypertrophy.
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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.