ArticleScience signaling2013
PLCε, PKD1, and SSH1L transduce RhoA signaling to protect mitochondria from oxidative stress in the heart.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 67 citations in OpenAlex.
- Phospholipases: Where Do We Stand?Methods in molecular biology (Clifton, N.J.) · 2027Review
- Structural insights into Phospholipase Cε activity and regulation.The Journal of biological chemistry · 2026Review
- Phospholipase C epsilon 1 as a therapeutic target in cardiovascular diseases.Journal of advanced research · 2025Review
- Cryo-EM structure of phospholipase Cε defines N-terminal domains and their roles in activity.Communications biology · 2025Article
- RhoA allosterically activates phospholipase Cε via its EF hands.Communications biology · 2025Article
- Reducing Cofilin dosage makes embryos resilient to heat stress.bioRxiv : the preprint server for biology · 2025Article
- The role of A-kinase anchoring proteins in cardiovascular diseases and recent advances.Frontiers in cell and developmental biology · 2025Review
- Untangling the role of RhoA in the heart: protective effect and mechanism.Cell death & disease · 2024Review
- Mechanical protein polycystin-1 directly regulates osteoclastogenesis and bone resorption.Science bulletin · 2024Article
- Anthracycline Toxicity: Light at the End of the Tunnel?Annual review of pharmacology and toxicology · 2024Review
- Role of G-protein coupled receptors in cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Molecular regulation of PLCβ signaling.Methods in enzymology · 2023Review
- RhoA signaling increases mitophagy and protects cardiomyocytes against ischemia by stabilizing PINK1 protein and recruiting Parkin to mitochondria.Cell death and differentiation · 2022Article
- Signaling pathways and targeted therapy for myocardial infarction.Signal transduction and targeted therapy · 2022Review
- Decoding the Cardiac Actions of Protein Kinase D Isoforms.Molecular pharmacology · 2021Review
- Review
- PKD1 alleviates oxidative stress-inhibited osteogenesis of rat bone marrow-derived mesenchymal stem cells through TAZ activation.Journal of cellular biochemistry · 2021Article
- Structure and regulation of phospholipase Cβ and ε at the membrane.Chemistry and physics of lipids · 2021Review
- Phosphorylated cofilin-2 is more prone to oxidative modifications on Cys39 and favors amyloid fibril formation.Redox biology · 2020Article
- Hydrogen Sulfide Therapy Suppresses Cofilin-2 and Attenuates Ischemic Heart Failure in a Mouse Model of Myocardial Infarction.Journal of cardiovascular pharmacology and therapeutics · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of the small guanosine triphosphatase RhoA can promote cell survival in cultured cardiomyocytes and in the heart. We showed that the circulating lysophospholipid sphingosine 1-phosphate (S1P), a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) agonist, signaled through RhoA and phospholipase Cε (PLCε) to increase the phosphorylation and activation of protein kinase D1 (PKD1). Genetic deletion of either PKD1 or its upstream regulator PLCε inhibited S1P-mediated cardioprotection against ischemia/reperfusion injury. Cardioprotection involved PKD1-mediated phosphorylation and inhibition of the cofilin phosphatase Slingshot 1L (SSH1L). Cofilin 2 translocates to mitochondria in response to oxidative stress or ischemia/reperfusion injury, and both S1P pretreatment and SSH1L knockdown attenuated translocation of cofilin 2 to mitochondria. Cofilin 2 associates with the proapoptotic protein Bax, and the mitochondrial translocation of Bax in response to oxidative stress was also attenuated by S1P treatment in isolated hearts or by knockdown of SSH1L or cofilin 2 in cardiomyocytes. Furthermore, SSH1L knockdown, like S1P treatment, increased cardiomyocyte survival and preserved mitochondrial integrity after oxidative stress. These findings reveal a pathway initiated by GPCR agonist-induced RhoA activation, in which PLCε signals to PKD1-mediated phosphorylation of cytoskeletal proteins to prevent the mitochondrial translocation and proapoptotic function of cofilin 2 and Bax and thereby promote cell survival.
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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.