ArticleProceedings of the National Academy of Sciences of the United States of America2013
Interference with ERK(Thr188) phosphorylation impairs pathological but not physiological cardiac hypertrophy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 84 citations in OpenAlex.
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- Python cardiomyocytes store lipids to buffer against hyperlipidemia.Annals of the New York Academy of Sciences · 2025Article
- Proteomic surveys of the mouse heart unveil cardiovascular responses to nitric oxide/cGMP signaling deficiencies.Communications biology · 2025Article
- Protective effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Canagliflozin combined with aerobic exercise protects against chronic heart failure in rats.iScience · 2024Article
- Review
- Central role for BRAF in cardiac hypertrophy: rethinking the pathological-physiological divide.Clinical science (London, England : 1979) · 2023Article
- Harnessing RKIP to Combat Heart Disease and Cancer.Cancers · 2022Review
- ERK1/2 Activity Is Critical for the Outcome of Ischemic Stroke.International journal of molecular sciences · 2022Article
- Effects of dim artificial light at night on locomotor activity, cardiovascular physiology, and circadian clock genes in a diurnal songbird.Environmental pollution (Barking, Essex : 1987) · 2021Article
- Integrated Quantitative Phosphoproteomics and Cell-based Functional Screening Reveals Specific Pathological Cardiac Hypertrophy-related Phosphorylation Sites.Molecules and cells · 2021Article
- Review
- Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1International journal of molecular sciences · 2021Article
- Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy.Molecules (Basel, Switzerland) · 2021Article
- CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor.Scientific reports · 2021Article
- Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure.Frontiers in cardiovascular medicine · 2021Article
- Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy.Cardiology journal · 2021Review
- ERK signalling: a master regulator of cell behaviour, life and fate.Nature reviews. Molecular cell biology · 2020Review
- Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy.The Journal of nutritional biochemistry · 2020Article
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9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are central mediators of cardiac hypertrophy and are discussed as potential therapeutic targets. However, direct inhibition of ERK1/2 leads to exacerbated cardiomyocyte death and impaired heart function. We have previously identified ERK(Thr188) autophosphorylation as a regulatory phosphorylation of ERK1/2 that is a key factor in cardiac hypertrophy. Here, we investigated whether interference with ERK(Thr188) phosphorylation permits the impairment of ERK1/2-mediated cardiac hypertrophy without increasing cardiomyocyte death. The impact of ERK(Thr188) phosphorylation on cardiomyocyte hypertrophy and cell survival was analyzed in isolated cells and in mice using the mutant ERK2(T188A), which is dominant-negative for ERK(Thr188) signaling. ERK2(T188A) efficiently attenuated cardiomyocyte hypertrophic responses to phenylephrine and to chronic pressure overload, but it affected neither antiapoptotic ERK1/2 signaling nor overall physiological cardiac function. In contrast to its inhibition of pathological hypertrophy, ERK2(T188A) did not interfere with physiological cardiac growth occurring with age or upon voluntary exercise. A preferential role of ERK(Thr188) phosphorylation in pathological types of hypertrophy was also seen in patients with aortic valve stenosis: ERK(Thr188) phosphorylation was increased 8.5 ± 1.3-fold in high-gradient, rapidly progressing cases (≥40 mmHg gradient), whereas in low-gradient, slowly progressing cases, the increase was not significant. Because interference with ERK(Thr188) phosphorylation (i) inhibits pathological hypertrophy and (ii) does not impair antiapoptotic ERK1/2 signaling and because ERK(Thr188) phosphorylation shows strong prevalence for aortic stenosis patients with rapidly progressing course, we conclude that interference with ERK(Thr188) phosphorylation offers the possibility to selectively address pathological types of cardiac hypertrophy.
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