ArticleThe Biochemical journal2006
High-affinity AKAP7delta-protein kinase A interaction yields novel protein kinase A-anchoring disruptor peptides.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- The optimal docking strength for reversibly tethered kinases.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Adrenergic Regulation of Calcium Channels in the Heart.Annual review of physiology · 2022Review
- Disruptors of AKAP-Dependent Protein-Protein Interactions.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Biochemical Analysis of AKAP-Anchored PKA Signaling Complexes.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
- Article
- Endothelial PKA activity regulates angiogenesis by limiting autophagy through phosphorylation of ATG16L1.eLife · 2019Article
- 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
- AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA.The Biochemical journal · 2016Article
- The Trafficking of the Water Channel Aquaporin-2 in Renal Principal Cells-a Potential Target for Pharmacological Intervention in Cardiovascular Diseases.Frontiers in pharmacology · 2016Review
- Neurochondrin is an atypical RIIα-specific A-kinase anchoring protein.Biochimica et biophysica acta · 2015Article
- A-kinase-anchoring proteins coordinate inflammatory responses to cigarette smoke in airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Selective disruption of the AKAP signaling complexes.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Highly functionalized terpyridines as competitive inhibitors of AKAP-PKA interactions.Angewandte Chemie (International ed. in English) · 2013Article
- Mechanism for targeting the A-kinase anchoring protein AKAP18δ to the membrane.The Journal of biological chemistry · 2012Article
- A key phosphorylation site in AC8 mediates regulation of Ca(2+)-dependent cAMP dynamics by an AC8-AKAP79-PKA signalling complex.Journal of cell science · 2012Article
- Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Molecular evolution of A-kinase anchoring protein (AKAP)-7: implications in comparative PKA compartmentalization.BMC evolutionary biology · 2012Article
- A-kinase anchoring proteins as potential drug targets.British journal of pharmacology · 2012Review
- A-kinase anchoring proteins: scaffolding proteins in the heart.American journal of physiology. Heart and circulatory physiology · 2011Review
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18 authors.
Funding
Abstract
PKA (protein kinase A) is tethered to subcellular compartments by direct interaction of its regulatory subunits (RI or RII) with AKAPs (A kinase-anchoring proteins). AKAPs preferentially bind RII subunits via their RII-binding domains. RII-binding domains form structurally conserved amphipathic helices with unrelated sequences. Their binding affinities for RII subunits differ greatly within the AKAP family. Amongst the AKAPs that bind RIIalpha subunits with high affinity is AKAP7delta [AKAP18delta; K(d) (equilibrium dissociation constant) value of 31 nM]. An N-terminally truncated AKAP7delta mutant binds RIIalpha subunits with higher affinity than the full-length protein presumably due to loss of an inhibitory region [Henn, Edemir, Stefan, Wiesner, Lorenz, Theilig, Schmidtt, Vossebein, Tamma, Beyermann et al. (2004) J. Biol. Chem. 279, 26654-26665]. In the present study, we demonstrate that peptides (25 amino acid residues) derived from the RII-binding domain of AKAP7delta bind RIIalpha subunits with higher affinity (K(d)=0.4+/-0.3 nM) than either full-length or N-terminally truncated AKAP7delta, or peptides derived from other RII binding domains. The AKAP7delta-derived peptides and stearate-coupled membrane-permeable mutants effectively disrupt AKAP-RII subunit interactions in vitro and in cell-based assays. Thus they are valuable novel tools for studying anchored PKA signalling. Molecular modelling indicated that the high affinity binding of the amphipathic helix, which forms the RII-binding domain of AKAP7delta, with RII subunits involves both the hydrophobic and the hydrophilic faces of the helix. Alanine scanning (25 amino acid peptides, SPOT technology, combined with RII overlay assays) of the RII binding domain revealed that hydrophobic amino acid residues form the backbone of the interaction and that hydrogen bond- and salt-bridge-forming amino acid residues increase the affinity of the interaction.
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