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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.
Journal ArticleDOI

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.
Journal ArticleDOI

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.
Journal ArticleDOI

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

Calcium pump of the plasma membrane is localized in caveolae.

TL;DR: The results demonstrate that the caveolae in various cells has the plasmalemmal Ca2+ pump as a common constituent, and it is inferred that the smooth plas malemmal invagination is an apparatus specialized for Ca2+, intake and extrusion from the cytoplasm.
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Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains.

TL;DR: Caveolar microdomains provide a scaffold for assembly of key Ca2+ signaling proteins into a complex and coordination of the molecular interactions leading to the activation of SOC, and it is shown that Trp1 is also localized in this microdomain where it interacts with one or more components of this complex, including IP3R3.
Journal ArticleDOI

Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs.

TL;DR: All three members of the Epac family regulate both Rap1 and Rap2, and it is concluded that the catalytic activity of Epac1 is constrained by a direct interaction between GEF and high affinity cAMP binding domains in the absence of cAMP.
Journal ArticleDOI

Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine.

TL;DR: It is concluded that MRP4 may influence diverse cellular processes regulated by cAMP and cGMP and that its substrate range is distinct from that of any other characterized MRP family member.
Journal ArticleDOI

Localization of cardiac L-type Ca2+ channels to a caveolar macromolecular signaling complex is required for β2-adrenergic regulation

TL;DR: It is demonstrated that a subpopulation of L-type Ca(2+) channels is localized to caveolae in ventricular myocytes as part of a macromolecular signaling complex necessary for beta(2)-adrenergic receptor (AR) regulation of I(Ca,L).
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