ArticleJournal of molecular biology2011
cAMP-dependent protein kinase A selects the excited state of the membrane substrate phospholamban.
Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 67 citations in OpenAlex.
- PLN-L31A/I40A for the treatment of inherited heart disease caused by PLN-R14del mutations.Acta pharmacologica Sinica · 2026Article
- Assessing the Function of Porcine A Kinase-Interacting Protein 1 (AKIP1) In Vitro-A Central Regulator of Oxidative Stress and Mitochondrial Functions.International journal of molecular sciences · 2025Article
- Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery.Cell reports. Medicine · 2023Article
- Ontogeny of cardiomyocytes: ultrastructure optimization to meet the demand for tight communication in excitation-contraction coupling and energy transfer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- Raf Kinase Inhibitory Protein regulates the cAMP-dependent protein kinase signaling pathway through a positive feedback loop.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Molecular noise filtering in the β-adrenergic signaling network by phospholamban pentamers.Cell reports · 2021Article
- Structural basis for allosteric control of the SERCA-Phospholamban membrane complex by CaeLife · 2021Article
- Structural Basis for GTP versus ATP Selectivity in the NMP Kinase AK3.Biochemistry · 2020Article
- Intrinsically disordered HAX-1 regulates CaBiochimica et biophysica acta. Biomembranes · 2020Article
- Dynamic allostery-based molecular workings of kinase:peptide complexes.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Review
- Probing membrane protein ground and conformationally excited states using dipolar- and J-coupling mediated MAS solid state NMR experiments.Methods (San Diego, Calif.) · 2018Review
- Effects of the Arg9Cys and Arg25Cys mutations on phospholamban's conformational equilibrium in membrane bilayers.Biochimica et biophysica acta. Biomembranes · 2018Article
- Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.Chemical reviews · 2018Review
- Capturing Invisible Motions in the Transition from Ground to Rare Excited States of T4 Lysozyme L99A.Biophysical journal · 2016Article
- Uncoupling Catalytic and Binding Functions in the Cyclic AMP-Dependent Protein Kinase A.Structure (London, England : 1993) · 2016Article
- Mechanism of cAMP Partial Agonism in Protein Kinase G (PKG).The Journal of biological chemistry · 2015Article
- Rats undernourished in utero have altered Ca2+ signaling and reduced fertility in adulthood.Physiological reports · 2015Article
- Structural basis for catalytically restrictive dynamics of a high-energy enzyme state.Nature communications · 2015Article
- A mechanism of global shape-dependent recognition and phosphorylation of filamin by protein kinase A.The Journal of biological chemistry · 2015Article
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7 authors at 1 institution in 1 country.
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Abstract
Phosphorylation of membrane proteins is a central regulatory and signaling mechanism across cell compartments. However, the recognition process and phosphorylation mechanism of membrane-bound substrates by kinases are virtually unknown. cAMP-dependent protein kinase A (PKA) is a ubiquitous enzyme that phosphorylates several soluble and membrane-bound substrates. In cardiomyocytes, PKA targets phospholamban (PLN), a membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA). In the unphosphorylated state, PLN binds SERCA, reducing the calcium uptake and generating muscle contraction. PKA phosphorylation of PLN at S16 in the cytoplasmic helix relieves SERCA inhibition, initiating muscle relaxation. Using steady-state kinetic assays, NMR spectroscopy, and molecular modeling, we show that PKA recognizes and phosphorylates the excited, membrane-detached R-state of PLN. By promoting PLN from a ground state to an excited state, we obtained a linear relationship between rate of phosphorylation and population of the excited state of PLN. The conformational equilibrium of PLN is crucial to regulate the extent of PLN phosphorylation and SERCA inhibition.
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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.