ArticleCardiovascular research2011
Enhanced activation of p21-activated kinase 1 in heart failure contributes to dephosphorylation of connexin 43.
Article in Cardiovascular research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Connexin 43 Phosphorylation: Implications in Multiple Diseases.Molecules (Basel, Switzerland) · 2023Review
- Serine-threonine protein phosphatase regulation of Cx43 dephosphorylation in arrhythmogenic disorders.Cellular signalling · 2021Review
- Molecular remodeling of Cx43, but not structural remodeling, promotes arrhythmias in an arrhythmogenic canine model of nonischemic heart failure.Journal of molecular and cellular cardiology · 2021Article
- Induction of Wnt signaling antagonists and p21-activated kinase enhances cardiomyocyte proliferation during zebrafish heart regeneration.Journal of molecular cell biology · 2021Article
- Alterations of housekeeping proteins in human aged and diseased hearts.Pflugers Archiv : European journal of physiology · 2021Article
- Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications.Pharmacological reviews · 2017Review
- Regulation of cardiac gap junctions by protein phosphatases.Journal of molecular and cellular cardiology · 2017Review
- Serine/Threonine Phosphatases in Atrial Fibrillation.Journal of molecular and cellular cardiology · 2017Review
- Murine Electrophysiological Models of Cardiac Arrhythmogenesis.Physiological reviews · 2017Review
- Roles and regulation of protein phosphatase 2A (PP2A) in the heart.Journal of molecular and cellular cardiology · 2016Review
- Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection.Pharmacology & therapeutics · 2015Review
- Counteracting Protein Kinase Activity in the Heart: The Multiple Roles of Protein Phosphatases.Frontiers in pharmacology · 2015Review
- Regulation of Ca(2+) transient by PP2A in normal and failing heart.Frontiers in physiology · 2015Review
- SR calcium handling dysfunction, stress-response signaling pathways, and atrial fibrillation.Frontiers in physiology · 2015Review
- Article
- Article
- Role of p21-activated kinases in cardiovascular development and function.Cellular and molecular life sciences : CMLS · 2013Review
- Unique catalytic activities and scaffolding of p21 activated kinase-1 in cardiovascular signaling.Frontiers in pharmacology · 2013Review
- Functional integrity of the T-tubular system in cardiomyocytes depends on p21-activated kinase 1.Journal of molecular and cellular cardiology · 2013Article
- Molecular mechanisms underlying cardiac protein phosphatase 2A regulation in heart.The Journal of biological chemistry · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
aimsWe previously showed decreased cellular coupling and dephosphorylation of the gap junctional protein connexin 43 (Cx43) in left ventricular (LV) myocytes from an arrhythmogenic rabbit model of non-ischaemic heart failure (HF) that was associated with a 2.5-fold increase in the amount of protein phosphatase type 2A (PP2A) co-localized with Cx43. Here, we further explore the molecular mechanisms of enhanced dephosphorylation of Cx43 in HF. p21-activated kinase 1 (PAK1) is a serine-threonine protein kinase that has been shown to activate PP2A. METHODS AND
resultsWe found that total PAK1 and activated PAK1 (PAK1-P(Thr423)) were both increased in HF rabbit LV (vs. controls). PAK1 co-immunoprecipitated (co-IP'd) with Cx43 protein and, with HF, co-IP'd PAK1 and PAK1-P(Thr423) were increased. With failing human LV, PAK1 total protein and PAK1-P(Thr423) were also increased globally and locally (co-IP'd with Cx43). To further explore the role of PAK1 in modulating Cx43 dephosphorylation and intercellular coupling, we overexpressed active PAK1 in isolated LV myocytes from control rabbits and in HEK293 cells with genetically modified overexpression of Cx43 (HEK293-Cx43). PAK1 overexpression in both rabbit myocytes and HEK293-Cx43 cells significantly increased PP2A activity (globally and at the level of Cx43), increased dephosphorylated Cx43, and markedly reduced intercellular dye coupling. These effects were attenuated with PP2A inhibition using okadaic acid (10 nM).
conclusionsPAK1 and PP2A are integral components of a macromolecular complex with cardiac Cx43, and increased activation of associated PAK1 can contribute to enhanced Cx43 dephosphorylation and impaired intercellular coupling that may underlie slow conduction in HF.
Indexed as
Identifiers
What OpenQuestion holds
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.