The biological functions of A-kinase anchor proteins

• Published in: Journal of molecular biology 2001-04, Vol.308 (2), p.99-114
• Main Authors: Feliciello, A, Gottesman, M E, Avvedimento, E V
• Format: Article
• Language: English
• Subjects: A Kinase Anchor Proteins; Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Cell Membrane - metabolism; Cell Nucleus - metabolism; Centrosome - metabolism; Cyclic AMP-Dependent Protein Kinases - chemistry; Cyclic AMP-Dependent Protein Kinases - metabolism; Cytoskeleton - metabolism; Endoplasmic Reticulum - metabolism; Humans; Mitochondria - metabolism; Molecular Sequence Data; Peroxisomes - metabolism; Receptors, Cell Surface - metabolism; Signal Transduction
• ISSN: 0022-2836
• DOI: 10.1006/jmbi.2001.4585

cAMP-dependent protein kinase is targeted to discrete subcellular locations by a family of specific anchor proteins (A-kinase anchor proteins, AKAPs). Localization recruits protein kinase A (PKA) holoenzyme close to its substrate/effector proteins, directing and amplifying the biological effects of cAMP signaling.AKAPs include two conserved structural modules: (i) a targeting domain that serves as a scaffold and membrane anchor; and (ii) a tethering domain that interacts with PKA regulatory subunits. Alternative splicing can shuffle targeting and tethering domains to generate a variety of AKAPs with different targeting specificity. Although AKAPs have been identified on the basis of their interaction with PKA, they also bind other signaling molecules, mainly phosphatases and kinases, that regulate AKAP targeting and activate other signal transduction pathways. We suggest that AKAP forms a "transduceosome" by acting as an autonomous multivalent scaffold that assembles and integrates signals derived from multiple pathways. The transduceosome amplifies cAMP and other signals locally and, by stabilizing and reducing the basal activity of PKA, it also exerts long-distance effects. The AKAP transduceosome thus optimizes the amplitude and the signal/noise ratio of cAMP-PKA stimuli travelling from the membrane to the nucleus and other subcellular compartments.