title: A-kinase anchoring proteins: cAMP compartmentalization in neurodegenerative and obstructive pulmonary diseases.
abstract: The universal second messenger cAMP is generated upon stimulation of Gs protein-coupled receptors, such as the β2 -adreneoceptor, and leads to the activation of PKA, the major cAMP effector protein. PKA oscillates between an on and off state and thereby regulates a plethora of distinct biological responses. The broad activation pattern of PKA and its contribution to several distinct cellular functions lead to the introduction of the concept of compartmentalization of cAMP. A-kinase anchoring proteins (AKAPs) are of central importance due to their unique ability to directly and/or indirectly interact with proteins that either determine the cellular content of cAMP, such as β2 -adrenoceptors, ACs and PDEs, or are regulated by cAMP such as the exchange protein directly activated by cAMP. We report on lessons learned from neurons indicating that maintenance of cAMP compartmentalization by AKAP5 is linked to neurotransmission, learning and memory. Disturbance of cAMP compartments seem to be linked to neurodegenerative disease including Alzheimer's disease. We translate this knowledge to compartmentalized cAMP signalling in the lung. Next to AKAP5, we focus here on AKAP12 and Ezrin (AKAP78). These topics will be highlighted in the context of the development of novel pharmacological interventions to tackle AKAP-dependent compartmentalization.
authors.affiliation: Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands; Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: Poppinga
authors.forename: P
authors.initials: P
authors.lastname: Muñoz-Llancao
authors.forename: C
authors.initials: C
authors.lastname: González-Billault
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008173:Lung Diseases, Obstructive / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D054758:A Kinase Anchor Proteins; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases