ArticleThe Biochemical journal2016
AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA.
Article in The Biochemical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- The evolution of AKAPs and emergence of PKA isotype selective anchoring determinants.The Journal of biological chemistry · 2025Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Advances in Protein Kinase Regulation of Stress Responses in Fruits and Vegetables.International journal of molecular sciences · 2025Review
- Structural basis of binding the unique N-terminal domain of microtubule-associated protein 2c to proteins regulating kinases of signaling pathways.The Journal of biological chemistry · 2024Article
- Phosphorylation, compartmentalization, and cardiac function.IUBMB life · 2023Article
- Disruptors of AKAP-Dependent Protein-Protein Interactions.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Beyond PKA: Evolutionary and structural insights that define a docking and dimerization domain superfamily.The Journal of biological chemistry · 2021Article
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- AKAP Signaling Islands: Venues for Precision Pharmacology.Trends in pharmacological sciences · 2020Review
- Article
- Small molecules for modulating the localisation of the water channel aquaporin-2-disease relevance and perspectives for targeting local cAMP signalling.Naunyn-Schmiedeberg's archives of pharmacology · 2019Review
- Structure and Functions of Microtubule Associated Proteins Tau and MAP2c: Similarities and Differences.Biomolecules · 2019Review
- Single nucleotide polymorphisms alter kinase anchoring and the subcellular targeting of A-kinase anchoring proteins.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Functionally specific binding regions of microtubule-associated protein 2c exhibit distinct conformations and dynamics.The Journal of biological chemistry · 2018Article
- Potential for therapeutic targeting of AKAP signaling complexes in nervous system disorders.Pharmacology & therapeutics · 2018Review
- Investigating PKA-RII specificity using analogs of the PKA:AKAP peptide inhibitor STAD-2.Bioorganic & medicinal chemistry · 2018Article
- Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System.Journal of cardiovascular development and disease · 2018Review
- Article
- Mechanisms for restraining cAMP-dependent protein kinase revealed by subunit quantitation and cross-linking approaches.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
A-kinase anchoring proteins (AKAPs) interact with the dimerization/docking (D/D) domains of regulatory subunits of the ubiquitous protein kinase A (PKA). AKAPs tether PKA to defined cellular compartments establishing distinct pools to increase the specificity of PKA signalling. Here, we elucidated the structure of an extended PKA-binding domain of AKAP18β bound to the D/D domain of the regulatory RIIα subunits of PKA. We identified three hydrophilic anchor points in AKAP18β outside the core PKA-binding domain, which mediate contacts with the D/D domain. Such anchor points are conserved within AKAPs that bind regulatory RII subunits of PKA. We derived a different set of anchor points in AKAPs binding regulatory RI subunits of PKA. In vitro and cell-based experiments confirm the relevance of these sites for the interaction of RII subunits with AKAP18 and of RI subunits with the RI-specific smAKAP. Thus we report a novel mechanism governing interactions of AKAPs with PKA. The sequence specificity of each AKAP around the anchor points and the requirement of these points for the tight binding of PKA allow the development of selective inhibitors to unequivocally ascribe cellular functions to the AKAP18-PKA and other AKAP-PKA interactions.
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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.