ArticleJournal of molecular and cellular cardiology2011
Ablation of p21-activated kinase-1 in mice promotes isoproterenol-induced cardiac hypertrophy in association with activation of Erk1/2 and inhibition of protein phosphatase 2A.
Article in Journal of molecular and cellular cardiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 60 citations in OpenAlex.
- Pak1 overexpression is associated with mild concentric cardiac remodeling and favorable systolic and diastolic functional indices in transgenic mice.Frontiers in cardiovascular medicine · 2026Article
- PAK1 (p21-Activated Kinase 1) and Its Role in Neurodevelopmental Disorders-New Case Report and a Comprehensive Review.International journal of molecular sciences · 2025Review
- Rac1 palmitoylation is required for cardiac stress adaptation and regulation of protein kinase A signaling.JCI insight · 2025Article
- P21-Activated Kinase 2 as a Novel Target for Ventricular Tachyarrhythmias Associated with Cardiac Adrenergic Stress and Hypertrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- p21-Activated Kinase 1 (Pak1) as an Element in Functional and Dysfunctional Interplay Among the Myocardium, Adipose Tissue, and Pancreatic Beta Cells.Comprehensive Physiology · 2025Review
- The role of ERK1/2 signaling in diabetes: pathogenic and therapeutic implications.Frontiers in pharmacology · 2025Review
- P21-activated kinase-1 signaling is required to preserve adipose tissue homeostasis and cardiac function.Molecular and cellular biochemistry · 2025Article
- NaResearch (Washington, D.C.) · 2025Article
- Transforming growth factor-β and bone morphogenetic protein signaling pathways in pathological cardiac hypertrophy.Cell cycle (Georgetown, Tex.) · 2023Review
- p21-activated kinase 1 (PAK1) as a therapeutic target for cardiotoxicity.Archives of toxicology · 2022Review
- Group I PAKs in myelin formation and repair of the central nervous system: what, when, and how.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Article
- Serine-threonine protein phosphatase regulation of Cx43 dephosphorylation in arrhythmogenic disorders.Cellular signalling · 2021Review
- CREG ameliorates the phenotypic switching of cardiac fibroblasts after myocardial infarction via modulation of CDC42.Cell death & disease · 2021Article
- Deletion of P21-activated kinase-1 induces age-dependent increased visceral adiposity and cardiac dysfunction in female mice.Molecular and cellular biochemistry · 2021Article
- Up-regulation of P21-activated kinase 1 in osteoarthritis chondrocytes is responsible for osteoarthritic cartilage destruction.Bioscience reports · 2020Article
- Effect of Triptolide on Temporal Expression of Cell Cycle Regulators During Cardiac Hypertrophy.Frontiers in pharmacology · 2020Article
- A high-throughput ratiometric method for imaging hypertrophic growth in cultured primary cardiac myocytes.Journal of molecular and cellular cardiology · 2019Article
- Solution structures and biophysical analysis of full-length group A PAKs reveal they are monomeric and auto-inhibited inThe Biochemical journal · 2019Article
- Loss of p21-activated kinase 1 (Pak1) promotes atrial arrhythmic activity.Heart rhythm · 2018Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Earlier investigations in our lab indicated an anti-adrenergic effect induced by activation of p21-activated kinase (Pak-1) and protein phosphatase 2A (PP2A). Our objective was to test the hypothesis that Pak-1/PP2A is a signaling cascade controlling stress-induced cardiac growth. We determined the effects of ablation of the Pak-1 gene on the response of the myocardium to chronic stress of isoproterenol (ISO) administration. Wild-type (WT) and Pak-1-knockout (Pak-1-KO) mice were randomized into six groups to receive either ISO, saline (CTRL), or ISO and FR180204, a selective inhibitor of Erk1/2. Echocardiography revealed that hearts of the Pak-1-KO/ISO group had increased LV fractional shortening, reduced LV chamber volume in diastole and systole, increased cardiac hypertrophy, and enhanced transmitral early filling deceleration time, compared to all other groups. The changes were associated with an increase in relative Erk1/2 activation in Pak-1-KO/ISO mice versus all other groups. ISO-induced cardiac hypertrophy and Erk1/2 activation in Pak-1-KO/ISO were attenuated when the selective Erk1/2 inhibitor FR180204 was administered. Immunoprecipitation showed an association between Pak-1, PP2A, and Erk1/2. Cardiac myocytes infected with an adenoviral vector expressing constitutively active Pak-1 showed a repression of Erk1/2 activation. p38 MAPK phosphorylation was decreased in Pak-1-KO/ISO and Pak-1-KO/CTRL mice compared to WT. Levels of phosphorylated PP2A were increased in ISO-treated Pak-1-KO mice, indicating reduced phosphatase activity. Maximum Ca(2+)-activated tension in detergent-extracted bundles of papillary fibers from ISO-treated Pak-1-KO mice was higher than in all other groups. Analysis of cTnI phosphorylation indicated that compared to WT, ISO-induced phosphorylation of cTnI was blunted in Pak-1-KO mice. Active Pak-1 is a natural inhibitor of Erk1/2 and a novel anti-hypertrophic signaling molecule upstream of PP2A.
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