A-kinase anchoring proteins: trafficking in G-protein-coupled receptors and the proteins that regulate receptor biology.
Scaffold proteins, such as members of the A-kinase anchoring protein (AKAP) family, constitute molecular 'tool boxes' that assist in modulating the amplitude, integration and transduction of information along signaling pathways. As AKAPs are multivalent and often display trafficking in response to the activation of a signaling pathway, each represents a scaffold with multiple, high-value targets for new drug discovery. Recent efforts at the molecular description of a subset of AKAPs that dynamically interact with members of the superfamily of G-protein-coupled receptors and ion channels provide an ideal starting point for drug discovery and development, one that has already produced a lead-like compound. Each of the docking sites for receptors/channels, protein kinases, phosphoprotein phosphatases and adaptor molecules may prove to be a suitable candidate for molecular description and for the identification of small molecules that can interfere with and/or modulate the activity of the overall signaling pathway, providing benefits to health or in treating disease states.
Malbon
Craig C
CC
Department of Pharmacology, Diabetes & Metabolic Diseases Research Program, School of Medicine, Stony Brook University, Stony Brook, NY 11794-8661, USA. craig@pharm.sunysb.edu
D054758:A Kinase Anchor Proteins / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction