ArticleProceedings of the National Academy of Sciences of the United States of America2002
MEKK1 is essential for cardiac hypertrophy and dysfunction induced by Gq.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 103 citations in OpenAlex.
- The intersection of disorders of sex development and cardiovascular diseases.Biology of sex differences · 2026Review
- Salvianolic acid B and Senkyunolide I synergistically alleviate cardiac hypertrophy and regulate MAP3K1 signaling.Chinese medicine · 2025Article
- Article
- α-Melanocyte-stimulating hormone alleviates pathological cardiac remodeling via melanocortin 5 receptor.EMBO reports · 2024Article
- Signaling cascades in the failing heart and emerging therapeutic strategies.Signal transduction and targeted therapy · 2022Review
- Role of miRNA-1 and miRNA-21 in Acute Myocardial Ischemia-Reperfusion Injury and Their Potential as Therapeutic Strategy.International journal of molecular sciences · 2022Review
- Application of microRNA Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease.Methods and protocols · 2020Article
- Identifying the key regulators that promote cell-cycle activity in the hearts of early neonatal pigs after myocardial injury.PloS one · 2020Article
- Functional significance of co-occurring mutations inOncotarget · 2018Article
- The p21-activated kinase 1 (Pak1) signalling pathway in cardiac disease: from mechanistic study to therapeutic exploration.British journal of pharmacology · 2018Review
- Natriuretic peptide receptor-C-mediated attenuation of vascular smooth muscle cell hypertrophy involves Gqα/PLCβ1 proteins and ROS-associated signaling.Pharmacology research & perspectives · 2018Article
- Cyclin D2 is a critical mediator of exercise-induced cardiac hypertrophy.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- MAP3K1 function is essential for cytoarchitecture of the mouse organ of Corti and survival of auditory hair cells.Disease models & mechanisms · 2015Article
- A RING to rule them all? Insights into the Map3k1 PHD motif provide a new mechanistic understanding into the diverse roles of Map3k1.Cell death and differentiation · 2015Review
- The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines.The EMBO journal · 2014Article
- Deciphering gene expression program of MAP3K1 in mouse eyelid morphogenesis.Developmental biology · 2013Article
- Signaling effectors underlying pathologic growth and remodeling of the heart.The Journal of clinical investigation · 2013Review
- Neuronostatin, a novel peptide encoded by somatostatin gene, regulates cardiac contractile function and cardiomyocyte survival.The Journal of biological chemistry · 2012Article
- Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale.Physiological reviews · 2010Review
- The role of MEKK1 in hypertrophic cardiomyopathy.International heart journal · 2010Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling via mitogen-activated protein kinases is implicated in heart failure induced by agonists for G protein-coupled receptors that act via the G protein Galphaq. However, this assertion relies heavily on pharmacological inhibitors and dominant-interfering proteins and not on gene deletion. Here, we show that endogenous cardiac MAPK/ERK kinase kinase-1 (MEKK1)/(MAP3K1), a mitogen-activated protein kinase kinase kinase, is activated by heart-restricted overexpression of Galphaq in mice. In cardiac myocytes derived from embryonic stem cells in culture, homozygous disruption of MEKK1 selectively impaired c-Jun N-terminal kinase activity in the absence or presence of phenlyephrine, a Galphaq-dependent agonist. Other terminal mitogen-activated protein kinases were unaffected. In mice, the absence of MEKK1 abolished the increase in cardiac mass, myocyte size, hypertrophy-associated atrial natriuretic factor induction, and c-Jun N-terminal kinase activation by Galphaq, and improved ventricular mechanical function. Thus, MEKK1 mediates cardiac hypertrophy induced by Galphaq in vivo and is a logical target for drug development in heart disease involving this pathway.
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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.