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Protein kinase A is central for forward transport of two-pore domain potassium channels K2P3.1 and K2P9.1.
Mant A
,
Elliott D
,
Eyers PA
,
O'Kelly IM
.
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Acid-sensitive two-pore domain potassium channels (K2P3.1 and K2P9.1) play key roles in both physiological and pathophysiological mechanisms, the most fundamental of which is control of resting membrane potential of cells in which they are expressed. These background "leak" channels are constitutively active once expressed at the plasma membrane, and hence tight control of their targeting and surface expression is fundamental to the regulation of K(+) flux and cell excitability. The chaperone protein, 14-3-3, binds to a critical phosphorylated serine in the channel C termini of K2P3.1 and K2P9.1 (Ser(393) and Ser(373), respectively) and overcomes retention in the endoplasmic reticulum by βCOP. We sought to identify the kinase responsible for phosphorylation of the terminal serine in human and rat variants of K2P3.1 and K2P9.1. Adopting a bioinformatic approach, three candidate protein kinases were identified: cAMP-dependent protein kinase, ribosomal S6 kinase, and protein kinase C. In vitro phosphorylation assays were utilized to determine the ability of the candidate kinases to phosphorylate the channel C termini. Electrophysiological measurements of human K2P3.1 transiently expressed in HEK293 cells and cell surface assays of GFP-tagged K2P3.1 and K2P9.1 enabled the determination of the functional implications of phosphorylation by specific kinases. All of our findings support the conclusion that cAMP-dependent protein kinase is responsible for the phosphorylation of the terminal serine in both K2P3.1 and K2P9.1.
Alcorta,
Sequence and expression of chicken and mouse rsk: homologs of Xenopus laevis ribosomal S6 kinase.
1989, Pubmed,
Xenbase
Alcorta,
Sequence and expression of chicken and mouse rsk: homologs of Xenopus laevis ribosomal S6 kinase.
1989,
Pubmed
,
Xenbase
Bayliss,
Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact.
2008,
Pubmed
Blom,
Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence.
2004,
Pubmed
Buckler,
An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells.
2000,
Pubmed
Coblitz,
C-terminal binding: an expanded repertoire and function of 14-3-3 proteins.
2006,
Pubmed
Czirják,
TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II.
2000,
Pubmed
,
Xenbase
Czirják,
Phosphorylation-dependent binding of 14-3-3 proteins controls TRESK regulation.
2008,
Pubmed
,
Xenbase
Duprat,
The TASK background K2P channels: chemo- and nutrient sensors.
2007,
Pubmed
Enyedi,
Molecular background of leak K+ currents: two-pore domain potassium channels.
2010,
Pubmed
Gao,
p90 ribosomal S6 kinase 1 (RSK1) and the catalytic subunit of protein kinase A (PKA) compete for binding the pseudosubstrate region of PKAR1alpha: role in the regulation of PKA and RSK1 activities.
2010,
Pubmed
Girard,
p11, an annexin II subunit, an auxiliary protein associated with the background K+ channel, TASK-1.
2002,
Pubmed
Kindler,
Local anesthetic inhibition of baseline potassium channels with two pore domains in tandem.
1999,
Pubmed
,
Xenbase
Kinoshita,
Phosphate-binding tag, a new tool to visualize phosphorylated proteins.
2006,
Pubmed
Lopes,
Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3.
2000,
Pubmed
,
Xenbase
Lu,
Reactive oxygen species-induced activation of p90 ribosomal S6 kinase prolongs cardiac repolarization through inhibiting outward K+ channel activity.
2008,
Pubmed
Medhurst,
Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery.
2001,
Pubmed
Moller,
Human rsk isoforms: cloning and characterization of tissue-specific expression.
1994,
Pubmed
Mrowiec,
14-3-3 proteins in membrane protein transport.
2006,
Pubmed
O'Kelly,
Forward transport. 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals.
2002,
Pubmed
O'Kelly,
Forward Transport of K2p3.1: mediation by 14-3-3 and COPI, modulation by p11.
2008,
Pubmed
,
Xenbase
Patel,
Inhalational anesthetics activate two-pore-domain background K+ channels.
1999,
Pubmed
Rajan,
Interaction with 14-3-3 proteins promotes functional expression of the potassium channels TASK-1 and TASK-3.
2002,
Pubmed
,
Xenbase
Roberts,
Effects of bisindolylmaleimide PKC inhibitors on p90RSK activity in vitro and in adult ventricular myocytes.
2005,
Pubmed
Sirois,
The TASK-1 two-pore domain K+ channel is a molecular substrate for neuronal effects of inhalation anesthetics.
2000,
Pubmed
Smith,
Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation.
2005,
Pubmed
Talley,
TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons.
2000,
Pubmed
Veale,
G(alpha)q-mediated regulation of TASK3 two-pore domain potassium channels: the role of protein kinase C.
2007,
Pubmed
Zuzarte,
Intracellular traffic of the K+ channels TASK-1 and TASK-3: role of N- and C-terminal sorting signals and interaction with 14-3-3 proteins.
2009,
Pubmed
,
Xenbase
van Heusden,
14-3-3 Proteins: insights from genome-wide studies in yeast.
2009,
Pubmed
