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Open AccessJournal ArticleDOI

Organization and Ca2+ Regulation of Adenylyl Cyclases in cAMP Microdomains

Debbie Willoughby, +1 more
- 01 Jul 2007 - 
- Vol. 87, Iss: 3, pp 965-1010
TLDR
The regulation of many of the ACs by the ubiquitous second messenger Ca(2+) provides an overarching mechanism for integrating the activities of these two major signaling systems, and cAMP will exhibit distinct kinetics in discrete cellular domains.
Abstract
The adenylyl cyclases are variously regulated by G protein subunits, a number of serine/threonine and tyrosine protein kinases, and Ca2+. In some physiological situations, this regulation can be re...

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Citations
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Principles of c-di-GMP signalling in bacteria.

TL;DR: This Review focuses on emerging principles of c-di-GMP signalling using selected systems in different bacteria as examples.
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A Coupled SYSTEM of Intracellular Ca2+ Clocks and Surface Membrane Voltage Clocks Controls the Timekeeping Mechanism of the Heart’s Pacemaker

TL;DR: Evidence is examined that forms the basis of this coupled-clock system concept in cardiac SANCs, where G protein-coupled receptors signaling creates pacemaker flexibility, ie, effects changes in the rhythmic action potential firing rate, by impacting on these very same factors that regulate robust basal coupled- clock system function.
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Caveolae as Organizers of Pharmacologically Relevant Signal Transduction Molecules

TL;DR: The role of Caveolae/caveolin in cardiac and pulmonary pathophysiology, pharmacologic implications of caveolar localization of signaling molecules, and the possibility that caveolae might serve as a therapeutic target are reviewed.
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Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown

TL;DR: Genes for these important regulatory enzymes are linked to schizophrenia, stroke and asthma, thus indicating the therapeutic potential that selective inhibitors could have as anti-inflammatory, anti-depressant and cognitive enhancer agents.
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Physiological roles for G protein-regulated adenylyl cyclase isoforms: insights from knockout and overexpression studies.

TL;DR: The latest on AC knockout and overexpression studies are explored to better understand the roles of G protein regulation of ACs in the brain, olfactory bulb, and heart.
References
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Journal ArticleDOI

Cyclic 3',5'-nucleotide phosphodiesterase. Demonstration of an activator.

TL;DR: In this paper, a mixture of a purified and a crude cyclic 3′,5′-nucleotide phosphodiesterase was shown to have higher activity than the summed activities of the individual preparations.
Journal ArticleDOI

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

TL;DR: 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.
Journal ArticleDOI

PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization.

TL;DR: PDE4 enzymes stand at a crossroads that allows them to integrate various signalling pathways with that of cAMP in spatially distinct compartments, and the recent elucidation of the structure of the PDE4 catalytic unit allows for molecular insight into the mode of catalysis as well as substrate and inhibitor selectivity.
Journal ArticleDOI

Crystal Structure of the Catalytic Domains of Adenylyl Cyclase in a Complex with Gsα·GTPγS

TL;DR: The crystal structure of a catalytically active form of adenylyl cyclase in a complex with its stimulatory heterotrimeric G protein α subunit (Gs α) and forskolin was determined to a resolution of 2.3 angstroms as discussed by the authors.
Journal ArticleDOI

Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins

TL;DR: What is known of the structure of the MRPs and the mechanisms by which they recognize and transport their diverse substrates are described and evidence that they may be involved in the clinical drug resistance of various forms of cancer is summarized.
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