Protein kinase A inhibits intermediate conductance Ca2+-activated K+ channels expressed in Xenopus oocytes

Pflügers Archiv : European journal of physiology
Craig B NeylonP H Reinhart

Abstract

Intermediate-conductance (IK) Ca(2+)-activated K(+) channels are expressed in many different cell types where they perform a variety of functions including cell volume regulation, transepithelial secretion, lymphocyte activation and cell cycle progression. IK channels are thought to be regulated by phosphorylation; however, whether kinases act directly on the channel is unclear. Using IK channels heterologously expressed in Xenopus oocytes, we demonstrate that IK channels are potently inhibited (60%) by the catalytic subunit of protein kinase A (PKA). Inhibition of IK channel current by PKA is abolished by mutation of four phosphorylation residues (S312, T327, S332, and T348) in the putative calmodulin-binding region of the channel. Evidence for direct modulation of the IK channel by PKA was further demonstrated using GST fusion proteins. The major site of phosphorylation was found to be serine 332; however, other residues were also phosphorylated. We conclude that IK channels can be directly regulated by the cAMP second-messenger system. The mechanism appears to involve direct phosphorylation by PKA of a modulatory locus in the cytoplasmic region of the channel, the site at which calmodulin is thought to interact. Modulation o...Continue Reading

References

Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·T M IshiiJ Maylie
Jan 31, 1998·The Journal of Biological Chemistry·N J LogsdonJ Aiyar
Aug 26, 1998·Pflügers Archiv : European journal of physiology·M Pellegrino, M Pellegrini
Feb 20, 1999·The Journal of Biological Chemistry·C M FangerJ Aiyar
Apr 28, 1999·Advances in Second Messenger and Phosphoprotein Research·I B Levitan
May 6, 1999·The Journal of General Physiology·D C DevorR J Bridges
Jan 5, 2000·The Journal of Biological Chemistry·A C GerlachD C Devor
Oct 21, 2000·Pflügers Archiv : European journal of physiology·R L SchrøderP Christophersen
Aug 10, 2001·The Journal of Biological Chemistry·W J JoinerL K Kaczmarek
Aug 18, 2001·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·T von HahnR Warth
Dec 19, 2001·Cellular Signalling·Knut Martin TorgersenKjetil Taskén
Jan 16, 2002·The Journal of Physiology·Fivos VogalisJohn B Furness
May 25, 2002·The Journal of Membrane Biology·A Wulf, A Schwab
Oct 16, 2002·Vascular Pharmacology·Craig B Neylon
May 6, 2003·Biochimica Et Biophysica Acta·Barbara Del CarloMario Pellegrino

❮ Previous
Next ❯

Citations

Sep 28, 2006·Annual Review of Physiology·Daniel Markovich, Peter S Aronson
Dec 8, 2006·American Journal of Physiology. Cell Physiology·Stella A NicolaouLaura Conforti
Jan 25, 2014·Pflügers Archiv : European journal of physiology·Lucie ClarysseChristophe Vandier
Mar 15, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shinkyu ChoiSuk Hyo Suh
May 2, 2006·Autonomic Neuroscience : Basic & Clinical·Craig B NeylonJohn B Furness
Aug 22, 2013·Channels·Mikio Hayashi, Ivana Novak
Mar 4, 2005·Journal of Cellular Physiology·A M PetrunkinaE Töpfer-Petersen
Apr 3, 2009·American Journal of Physiology. Cell Physiology·Man ZhangYan-Ai Mei
Nov 15, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ameet A ChimoteLaura Conforti
Jun 5, 2012·The Journal of Experimental Biology·Kevin M CrispKaren A Mesce

❮ Previous
Next ❯

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.