Protein kinase a modulates plc-dependent regulation and PIP2-sensitivity of K+ channels

Coeli M.B. Lopes, Juan I. Remon, Alessandra Matavel, Jin Liang Sui, Inna Keselman, Emiliano Medei, Yuming Shen, Avia Rosenhouse-Dantsker, Tibor Rohacs, Diomedes E. Logothetis

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Neurotransmitter and hormone regulation of cellular function can result from a concomitant stimulation of different signaling pathways. Signaling cascades are strongly regulated during disease and are often targeted by commonly used drugs. Crosstalk of different signaling pathways can have profound effects on the regulation of cell excitability. Members of all the three main structural families of potassium channels: inward-rectifiers, voltage-gated and 2-P domain, have been shown to be regulated by direct phosphorylation and Gq-coupled receptor activation. Here we test members of each of the three families, Kir3.1/Kir3.4, KCNQ1/KCNE1 and TREK-1 channels, all of which have been shown to be regulated directly by phosphatidylinositol bisphosphate (PIP2). The three channels are inhibited by activation of Gq-coupled receptors and are differentially regulated by protein kinase A (PKA). We show that Gq-coupled receptor regulation can be physiologically modulated directly through specific channel phosphorylation sites. Our results suggest that PKA phosphorylation of these channels affects Gq-coupled receptor inhibition through modulation of the channel sensitivity to PIP2.

Original languageEnglish (US)
Pages (from-to)124-134
Number of pages11
JournalChannels
Volume1
Issue number2
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Fingerprint

Phosphorylation
Protein Kinases
Cyclic AMP-Dependent Protein Kinases
Chemical activation
Inwardly Rectifying Potassium Channel
Crosstalk
Phosphatidylinositols
Neurotransmitter Agents
Cells
Modulation
Hormones
Electric potential
Pharmaceutical Preparations

Keywords

  • Forskolin
  • G proteinsensitive inwardly rectifying K channels (Kir3)
  • H89
  • KCNQ1/KCNE1 channels
  • Phosphatidyl inositol-bis-phosphate (PIP2)
  • Phosphorylation sites
  • PLC-dependent inhibition
  • Protein Kinase A (PKA)
  • TREK1 channels

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

Lopes, C. M. B., Remon, J. I., Matavel, A., Sui, J. L., Keselman, I., Medei, E., ... Logothetis, D. E. (2007). Protein kinase a modulates plc-dependent regulation and PIP2-sensitivity of K+ channels. Channels, 1(2), 124-134. https://doi.org/10.4161/chan.4322

Protein kinase a modulates plc-dependent regulation and PIP2-sensitivity of K+ channels. / Lopes, Coeli M.B.; Remon, Juan I.; Matavel, Alessandra; Sui, Jin Liang; Keselman, Inna; Medei, Emiliano; Shen, Yuming; Rosenhouse-Dantsker, Avia; Rohacs, Tibor; Logothetis, Diomedes E.

In: Channels, Vol. 1, No. 2, 01.01.2007, p. 124-134.

Research output: Contribution to journalArticle

Lopes, CMB, Remon, JI, Matavel, A, Sui, JL, Keselman, I, Medei, E, Shen, Y, Rosenhouse-Dantsker, A, Rohacs, T & Logothetis, DE 2007, 'Protein kinase a modulates plc-dependent regulation and PIP2-sensitivity of K+ channels', Channels, vol. 1, no. 2, pp. 124-134. https://doi.org/10.4161/chan.4322
Lopes, Coeli M.B. ; Remon, Juan I. ; Matavel, Alessandra ; Sui, Jin Liang ; Keselman, Inna ; Medei, Emiliano ; Shen, Yuming ; Rosenhouse-Dantsker, Avia ; Rohacs, Tibor ; Logothetis, Diomedes E. / Protein kinase a modulates plc-dependent regulation and PIP2-sensitivity of K+ channels. In: Channels. 2007 ; Vol. 1, No. 2. pp. 124-134.
@article{c9ceb3010ccc49099bcd87efaa445c13,
title = "Protein kinase a modulates plc-dependent regulation and PIP2-sensitivity of K+ channels",
abstract = "Neurotransmitter and hormone regulation of cellular function can result from a concomitant stimulation of different signaling pathways. Signaling cascades are strongly regulated during disease and are often targeted by commonly used drugs. Crosstalk of different signaling pathways can have profound effects on the regulation of cell excitability. Members of all the three main structural families of potassium channels: inward-rectifiers, voltage-gated and 2-P domain, have been shown to be regulated by direct phosphorylation and Gq-coupled receptor activation. Here we test members of each of the three families, Kir3.1/Kir3.4, KCNQ1/KCNE1 and TREK-1 channels, all of which have been shown to be regulated directly by phosphatidylinositol bisphosphate (PIP2). The three channels are inhibited by activation of Gq-coupled receptors and are differentially regulated by protein kinase A (PKA). We show that Gq-coupled receptor regulation can be physiologically modulated directly through specific channel phosphorylation sites. Our results suggest that PKA phosphorylation of these channels affects Gq-coupled receptor inhibition through modulation of the channel sensitivity to PIP2.",
keywords = "Forskolin, G proteinsensitive inwardly rectifying K channels (Kir3), H89, KCNQ1/KCNE1 channels, Phosphatidyl inositol-bis-phosphate (PIP2), Phosphorylation sites, PLC-dependent inhibition, Protein Kinase A (PKA), TREK1 channels",
author = "Lopes, {Coeli M.B.} and Remon, {Juan I.} and Alessandra Matavel and Sui, {Jin Liang} and Inna Keselman and Emiliano Medei and Yuming Shen and Avia Rosenhouse-Dantsker and Tibor Rohacs and Logothetis, {Diomedes E.}",
year = "2007",
month = "1",
day = "1",
doi = "10.4161/chan.4322",
language = "English (US)",
volume = "1",
pages = "124--134",
journal = "Channels",
issn = "1933-6950",
publisher = "Landes Bioscience",
number = "2",

}

TY - JOUR

T1 - Protein kinase a modulates plc-dependent regulation and PIP2-sensitivity of K+ channels

AU - Lopes, Coeli M.B.

AU - Remon, Juan I.

AU - Matavel, Alessandra

AU - Sui, Jin Liang

AU - Keselman, Inna

AU - Medei, Emiliano

AU - Shen, Yuming

AU - Rosenhouse-Dantsker, Avia

AU - Rohacs, Tibor

AU - Logothetis, Diomedes E.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Neurotransmitter and hormone regulation of cellular function can result from a concomitant stimulation of different signaling pathways. Signaling cascades are strongly regulated during disease and are often targeted by commonly used drugs. Crosstalk of different signaling pathways can have profound effects on the regulation of cell excitability. Members of all the three main structural families of potassium channels: inward-rectifiers, voltage-gated and 2-P domain, have been shown to be regulated by direct phosphorylation and Gq-coupled receptor activation. Here we test members of each of the three families, Kir3.1/Kir3.4, KCNQ1/KCNE1 and TREK-1 channels, all of which have been shown to be regulated directly by phosphatidylinositol bisphosphate (PIP2). The three channels are inhibited by activation of Gq-coupled receptors and are differentially regulated by protein kinase A (PKA). We show that Gq-coupled receptor regulation can be physiologically modulated directly through specific channel phosphorylation sites. Our results suggest that PKA phosphorylation of these channels affects Gq-coupled receptor inhibition through modulation of the channel sensitivity to PIP2.

AB - Neurotransmitter and hormone regulation of cellular function can result from a concomitant stimulation of different signaling pathways. Signaling cascades are strongly regulated during disease and are often targeted by commonly used drugs. Crosstalk of different signaling pathways can have profound effects on the regulation of cell excitability. Members of all the three main structural families of potassium channels: inward-rectifiers, voltage-gated and 2-P domain, have been shown to be regulated by direct phosphorylation and Gq-coupled receptor activation. Here we test members of each of the three families, Kir3.1/Kir3.4, KCNQ1/KCNE1 and TREK-1 channels, all of which have been shown to be regulated directly by phosphatidylinositol bisphosphate (PIP2). The three channels are inhibited by activation of Gq-coupled receptors and are differentially regulated by protein kinase A (PKA). We show that Gq-coupled receptor regulation can be physiologically modulated directly through specific channel phosphorylation sites. Our results suggest that PKA phosphorylation of these channels affects Gq-coupled receptor inhibition through modulation of the channel sensitivity to PIP2.

KW - Forskolin

KW - G proteinsensitive inwardly rectifying K channels (Kir3)

KW - H89

KW - KCNQ1/KCNE1 channels

KW - Phosphatidyl inositol-bis-phosphate (PIP2)

KW - Phosphorylation sites

KW - PLC-dependent inhibition

KW - Protein Kinase A (PKA)

KW - TREK1 channels

UR - http://www.scopus.com/inward/record.url?scp=36348969179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36348969179&partnerID=8YFLogxK

U2 - 10.4161/chan.4322

DO - 10.4161/chan.4322

M3 - Article

C2 - 18690021

AN - SCOPUS:36348969179

VL - 1

SP - 124

EP - 134

JO - Channels

JF - Channels

SN - 1933-6950

IS - 2

ER -