Journal article
Abstract P2083: Erk-mediated Phosphorylation Of Grk2 Leads To Reduced Pyruvate Dehydrogenase Activity And Alters Pyroptotic Signaling
Circulation research, v 131(Suppl_1), pAP2083
05 Aug 2022
Abstract
G protein-coupled receptors (GPCRs) are important regulators of cellular functions where agonist binding leads to receptor conformational changes and downstream activation of g-protein-mediated signaling cascades. Signal transduction is terminated by receptor phosphorylation mediated by G-protein coupled receptor kinases (GRKs). GPCR kinase 2 (GRK2) is a main GRK in the heart and is upregulated in heart failure (HF) patients. Recently, we and others have shown that GRK2 can translocate to cardiac mitochondria where it regulates metabolism. Notably, we found that phosphorylated GRK2 at S670 post- ischemia/reperfusion (IR) decreases glucose mitochondrial utilization and pyruvate dehydrogenase (PDH) activity. Furthermore, 2D-SDS PAGE followed by LC/MS/MS revealed a potential link between mitochondrial GRK2 and PDH phosphorylation. Using a novel PDHα KI CRISPR Cas HEK cell line, we tested the hypothesize that PDH phosphorylation of this novel site was important for PDH activity. Utilizing cytosolic and mitochondrially-targeted pyruvate indicators we measured pyruvate levels in WT and KI HEK cells. In parallel, using a novel mouse model GRK2-S670A, we investigated the role of ERK in mediating GRK2 mitochondrial translocation and pyroptotic signaling. Further experiments will determine long-term impact of mitochondrial GRK2 in cell survival in cardiac pathological conditions.
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Details
- Title
- Abstract P2083: Erk-mediated Phosphorylation Of Grk2 Leads To Reduced Pyruvate Dehydrogenase Activity And Alters Pyroptotic Signaling
- Creators
- Ruxu Zhai - Drexel UniversitySarah Montgomery - Drexel UniversityTian Yuzhen - Drexel UniversityEmad Alnemri - Thomas Jefferson UniversityHsin Yao tang - The Wistar InstitutePriscila Sato - Drexel University
- Publication Details
- Circulation research, v 131(Suppl_1), pAP2083
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000899250500093
- Other Identifier
- 991020112215104721
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Hematology
- Peripheral Vascular Disease