Localized Effects of cAMP Mediated by Distinct Routes of Protein Kinase A

• Published in: Physiological reviews 2004-01, Vol.84 (1), p.137-167
• Main Authors: TASKEN, KJETIL, AANDAHL, EINAR MARTIN
• Format: Article
• Language: English
• Subjects: Animals; Carrier Proteins - chemistry; Carrier Proteins - physiology; Cellular biology; Cyclic adenylic acid; Cyclic AMP - physiology; Cyclic AMP-Dependent Protein Kinases - physiology; Cyclin-dependent kinases; Gene Expression Regulation - physiology; Genomics; Humans; Physiological aspects; Protein kinases; Proteins; Signal Transduction - physiology
• ISSN: 0031-9333; 1522-1210
• DOI: 10.1152/physrev.00021.2003

The Biotechnology Centre of Oslo, University of Oslo, Norway Taskén, Kjetil, and Einar Martin Aandahl. Localized Effects of cAMP Mediated by Distinct Routes of Protein Kinase A. Physiol Rev 84: 137–167, 2004; 10.1152/physrev.00021.2003.—More than 20% of the human genome encodes proteins involved in transmembrane and intracellular signaling pathways. The cAMP-protein kinase A (PKA) pathway is one of the most common and versatile signal pathways in eukaryotic cells and is involved in regulation of cellular functions in almost all tissues in mammals. Various extracellular signals converge on this signal pathway through ligand binding to G protein-coupled receptors, and the cAMP-PKA pathway is therefore tightly regulated at several levels to maintain specificity in the multitude of signal inputs. Ligand-induced changes in cAMP concentration vary in duration, amplitude, and extension into the cell, and cAMP microdomains are shaped by adenylyl cyclases that form cAMP as well as phosphodiesterases that degrade cAMP. Different PKA isozymes with distinct biochemical properties and cell-specific expression contribute to cell and organ specificity. A kinase anchoring proteins (AKAPs) target PKA to specific substrates and distinct subcellular compartments providing spatial and temporal specificity for mediation of biological effects channeled through the cAMP-PKA pathway. AKAPs also serve as scaffolding proteins that assemble PKA together with signal terminators such as phosphatases and cAMP-specific phosphodiesterases as well as components of other signaling pathways into multiprotein signaling complexes that serve as crossroads for different paths of cell signaling. Targeting of PKA and integration of a wide repertoire of proteins involved in signal transduction into complex signal networks further increase the specificity required for the precise regulation of numerous cellular and physiological processes. Address for reprint requests and other correspondence: K. Taskén, The Biotechnology Centre of Oslo, Univ. of Oslo, PO Box 1125 Blindern, N-0317 Oslo, Norway (E-mail: kjetil.tasken{at}biotek.uio.no ).