title: Pharmacological targeting of AKAP-directed compartmentalized cAMP signalling.
abstract: The second messenger cyclic adenosine monophosphate (cAMP) can bind and activate protein kinase A (PKA). The cAMP/PKA system is ubiquitous and involved in a wide array of biological processes and therefore requires tight spatial and temporal regulation. Important components of the safeguard system are the A-kinase anchoring proteins (AKAPs), a heterogeneous family of scaffolding proteins defined by its ability to directly bind PKA. AKAPs tether PKA to specific subcellular compartments, and they bind further interaction partners to create local signalling hubs. The recent discovery of new AKAPs and advances in the field that shed light on the relevance of these hubs for human disease highlight unique opportunities for pharmacological modulation. This review exemplifies how interference with signalling, particularly cAMP signalling, at such hubs can reshape signalling responses and discusses how this could lead to novel pharmacological concepts for the treatment of disease with an unmet medical need such as cardiovascular disease and cancer.
authors.affiliation: Max Delbrück Center for Molecular Medicine Berlin in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dema
authors.affiliation: Max Delbrück Center for Molecular Medicine Berlin in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Perets
authors.affiliation: Max Delbrück Center for Molecular Medicine Berlin in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany.
authors.forename: Maike Svenja
authors.initials: MS
authors.lastname: Schulz
authors.affiliation: Max Delbrück Center for Molecular Medicine Berlin in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany.
authors.forename: Veronika Anita
authors.initials: VA
authors.lastname: Deák
authors.affiliation: Max Delbrück Center for Molecular Medicine Berlin in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany; DZHK, German Centre for Cardiovascular Research, Oudenarder Straße 16, 13347 Berlin, Germany. Electronic address: enno.klussmann@mdc-berlin.de.
authors.forename: Enno
authors.initials: E
authors.lastname: Klussmann
mesh_terms: D054758:A Kinase Anchor Proteins / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D017124:Conserved Sequence; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D060066:Protein Interaction Maps; D015290:Second Messenger Systems
chemical_list: D054758:A Kinase Anchor Proteins; D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: A-kinase anchoring protein; Cancer; Cardiovascular; Protein kinase A; Protein–protein interaction