"Shaping" of cell signaling via AKAP-tethered PDE4D: Probing with AKAR2-AKAP5 biosensor.

Journal of Molecular Signaling
Salih S KoçerCraig C Malbon

Abstract

PKA, a key regulator of cell signaling, phosphorylates a diverse and important array of target molecules and is spatially docked to members of the A-kinase Anchoring Protein (AKAP) family. AKAR2 is a biosensor which yields a FRET signal in vivo, when phosphorylated by PKA. AKAP5, a prominent member of the AKAP family, docks several signaling molecules including PKA, PDE4D, as well as GPCRs, and is obligate for the propagation of the activation of the mitogen-activated protein kinase cascade from GPCRs to ERK1,2. Using an AKAR2-AKAP5 fusion "biosensor", we investigated the spatial-temporal activation of AKAP5 undergoing phosphorylation by PKA in response to β-adrenergic stimulation. The pattern of PKA activation reported by AKAR2-AKAP5 is a more rapid and spatially distinct from those "sensed" by AKAR2-AKAP12. Spatial-temporal restriction of activated PKA by AKAP5 was found to "shape" the signaling response. Phosphatase PDE4D tethered to AKAP5 also later reverses within 60 s elevated intracellular cyclic AMP levels stimulated by β-adrenergic agonist. AKAP12, however, fails to attenuate the rise in cyclic AMP over this time. Fusion of the AKAP5 PDE4D-binding-domain to AKAP12 was found to accelerate a reversal of accumulation of ...Continue Reading

References

Feb 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·R N FabricantG J Todaro
Jan 1, 1991·The International Journal of Biochemistry·H Y WangC C Malbon
Feb 21, 1997·The Journal of Biological Chemistry·S VijayaraghavanD W Carr
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·K A BurtonG S McKnight
May 26, 1998·The EMBO Journal·M L Dell'AcquaJ D Scott
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·J ZhangR Y Tsien
Dec 4, 2002·Nature Reviews. Molecular Cell Biology·Jin ZhangRoger Y Tsien
Dec 2, 2004·Nature Reviews. Molecular Cell Biology·Wei Wong, John D Scott
Mar 23, 2005·Current Opinion in Cell Biology·George S Baillie, Miles D Houslay
Apr 28, 2006·The EMBO Journal·Debbie WilloughbyDermot M F Cooper
May 13, 2006·Trends in Biochemical Sciences·F Donelson SmithJohn D Scott
Jun 10, 2006·The Journal of Biological Chemistry·Jiangchuan TaoCraig C Malbon
Jul 1, 2006·Trends in Molecular Medicine·George McConnachieJohn D Scott
Jan 6, 2009·Journal of Applied Microbiology·S S KoçerS R Simon
Jan 26, 2010·PLoS Computational Biology·Sharat J VayttadenRichard B Clark
Apr 24, 2010·Journal of Molecular Signaling·Jiangchuan TaoCraig C Malbon
May 11, 2011·Journal of Molecular Signaling·Shujuan GaoCraig C Malbon
Jul 21, 2011·The Journal of Biological Chemistry·Ilse Delint-RamirezDermot M F Cooper
Aug 13, 2011·Journal of Molecular Signaling·Shujuan GaoCraig C Malbon

❮ Previous
Next ❯

Citations

Dec 7, 2013·Endocrine Reviews·Monalisa F AzevedoConstantine A Stratakis

❮ Previous
Next ❯

Methods Mentioned

BETA
biosensor
biosenses
electrophoresis
biosensing
FRET
biosensors
transfection
pull-downs
PCR

Software Mentioned

METAFLUOR

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2021 Meta ULC. All rights reserved