ArticleAmerican journal of physiology. Heart and circulatory physiology2012
p21-activated kinase improves cardiac contractility during ischemia-reperfusion concomitant with changes in troponin-T and myosin light chain 2 phosphorylation.
Article in American journal of physiology. Heart and circulatory physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 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 Promotes Gluconeogenesis Via the ACSS2/KAT2A/PCK1 Complex to Attenuate Steatotic Liver Ischemia-Reperfusion Injury.International journal of biological sciences · 2026Article
- Modulating PAK1: Accessory Proteins as Promising Therapeutic Targets.Biomolecules · 2025Review
- P21-activated kinase-1 signaling is required to preserve adipose tissue homeostasis and cardiac function.Molecular and cellular biochemistry · 2025Article
- Testosterone acts through the membrane protein GPRC6A to cause cardiac edema in zebrafish embryos.Development (Cambridge, England) · 2024Article
- Targeting p21-activated kinase 1 for development of a novel anti-arrhythmic drug class.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- The role of P21-activated kinase (Pak1) in sinus node function.Journal of molecular and cellular cardiology · 2023Article
- Brugada Syndrome: Warning of a Systemic Condition?Frontiers in cardiovascular medicine · 2021Review
- 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
- The p21-activated kinase 1 (Pak1) signalling pathway in cardiac disease: from mechanistic study to therapeutic exploration.British journal of pharmacology · 2018Review
- Characteristics of mRNA dynamic expression related to spinal cord ischemia/reperfusion injury: a transcriptomics study.Neural regeneration research · 2016Article
- Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype.Frontiers in physiology · 2016Review
- Reduction of apoptosis and preservation of mitochondrial integrity under ischemia/reperfusion injury is mediated by estrogen receptor β.Biology of sex differences · 2016Article
- Knockout of p21-activated kinase-1 attenuates exercise-induced cardiac remodelling through altered calcineurin signalling.Cardiovascular research · 2015Article
- PAK1 is a novel cardiac protective signaling molecule.Frontiers of medicine · 2014Review
- P21-activated kinase in inflammatory and cardiovascular disease.Cellular signalling · 2014Review
- The art of the deal in myofilament modulation of function.Journal of molecular and cellular cardiology · 2014Article
- p21-Activated kinase1 (Pak1) is a negative regulator of NADPH-oxidase 2 in ventricular myocytes.Journal of molecular and cellular cardiology · 2014Article
- Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review.Frontiers in physiology · 2014Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
p21-activated kinase 1 (Pak1) is a serine/threonine kinase that activates protein phosphatase 2a, resulting in the dephosphorylation of cardiac proteins and increased myofilament Ca(2+) sensitivity. Emerging evidence indirectly indicates a role for Pak1 in ischemia-reperfusion (I/R), but direct evidence is lacking. We hypothesize that activation of the Pak1 signaling pathway is a cardioprotective mechanism that prevents or reverses the detrimental effects of ischemic injury by inducing posttranslational modifications in myofilament proteins that ultimately improve cardiac contractility following ischemic insult. In the present study, we subjected ex vivo hearts from wild-type (WT) and Pak1-knockout (KO) mice to 20 min of global cardiac ischemia followed by 30 min of reperfusion. In the absence of Pak1, there was an exacerbation of the increased end-diastolic pressure and reduced left ventricular developed pressure occurring after I/R injury. ProQ analysis revealed an increase in troponin-T phosphorylation at baseline in Pak1-KO hearts compared with WT. Significantly decreased myosin light chain 2 (MLC2) phosphorylation in Pak1-KO hearts compared with WT after I/R injury was confirmed by Western immunoblotting. These data indicate that Pak1-KO hearts have reduced recovery of myocardial performance after global I/R injury concomitant with changes in troponin-T and MLC2 phosphorylation. Finally, a protein-protein association between Pak1 and MLC2, and Pak1 and troponin-T, was determined by coimmunoprecipitation. Thus, results of our study provide a basis for targeting a novel pathway, including Pak1, in the therapies for patients with ischemic events.
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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.