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Protein kinase C dependent inhibition of the heteromeric Kir4.1-Kir5.1 channel.
Rojas A
,
Cui N
,
Su J
,
Yang L
,
Muhumuza JP
,
Jiang C
.
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Heteromultimerization of Kir4.1 and Kir5.1 leads to a channel with distinct functional properties. The heteromeric Kir4.1-Kir5.1 channel is expressed in the eye, kidney and brainstem and has CO(2)/pH sensitivity in the physiological range, suggesting a candidate molecule for the regulation of K(+) homeostasis and central CO(2) chemoreception. It is known that K(+) transport in renal epithelium and brainstem CO(2) chemosensitivity are subject to modulation by hormones and neurotransmitters that activate distinct intracellular signaling pathways. If the Kir4.1-Kir5.1 channel is involved in pH-dependent regulation of cellular functions, it may also be regulated by some of the intracellular signaling systems. Therefore, we undertook studies to determine whether PKC modulates the heteromeric Kir4.1-Kir5.1 channel. The channel expressed using a Kir4.1-Kir5.1 tandem dimer construct was inhibited by the PKC activator PMA in a dose-dependent manner. The channel inhibition was produced via reduction of the P(open). The effect of PMA was abolished by specific PKC inhibitors. In contrast, exposure of oocytes to forskolin (a PKA activator) had no significant effect on Kir4.1-Kir5.1 currents. The channel inhibition appeared to be independent of PIP(2) depletion and PKC-dependent internalization. Several consensus sequences of potential PKC phosphorylation sites were identified in the Kir4.1 and Kir5.1 subunits by sequence scan. Although the C-terminal peptides of both Kir4.1 and Kir5.1 were phosphorylated in vitro, site-directed mutagenesis of individual residues failed to reveal the PKC phosphorylation sites suggesting that the channel may have multiple phosphorylation sites. Taken together, these results suggest that the Kir4.1-Kir5.1 but not the homomeric Kir4.1 channel is strongly inhibited by PKC activation.
Béguin,
PKA-mediated phosphorylation of the human K(ATP) channel: separate roles of Kir6.2 and SUR1 subunit phosphorylation.
1999, Pubmed,
Xenbase
Béguin,
PKA-mediated phosphorylation of the human K(ATP) channel: separate roles of Kir6.2 and SUR1 subunit phosphorylation.
1999,
Pubmed
,
Xenbase
Casamassima,
Identification of a heteromeric interaction that influences the rectification, gating, and pH sensitivity of Kir4.1/Kir5.1 potassium channels.
2003,
Pubmed
,
Xenbase
Cui,
Modulation of the heteromeric Kir4.1-Kir5.1 channels by P(CO(2)) at physiological levels.
2001,
Pubmed
,
Xenbase
Du,
Characteristic interactions with phosphatidylinositol 4,5-bisphosphate determine regulation of kir channels by diverse modulators.
2004,
Pubmed
,
Xenbase
Fakler,
Kir2.1 inward rectifier K+ channels are regulated independently by protein kinases and ATP hydrolysis.
1994,
Pubmed
,
Xenbase
Feldman,
Breathing: rhythmicity, plasticity, chemosensitivity.
2003,
Pubmed
Henry,
Protein kinase C inhibition of cloned inward rectifier (HRK1/KIR2.3) K+ channels expressed in Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Hibino,
Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes.
2004,
Pubmed
Hibino,
Expression of an inwardly rectifying K(+) channel, Kir4.1, in satellite cells of rat cochlear ganglia.
1999,
Pubmed
Higashi,
An inwardly rectifying K(+) channel, Kir4.1, expressed in astrocytes surrounds synapses and blood vessels in brain.
2001,
Pubmed
Ishii,
Differential expression and distribution of Kir5.1 and Kir4.1 inwardly rectifying K+ channels in retina.
2003,
Pubmed
Ito,
Immunolocalization of an inwardly rectifying K+ channel, K(AB)-2 (Kir4.1), in the basolateral membrane of renal distal tubular epithelia.
1996,
Pubmed
Jiang,
An alternative approach to the identification of respiratory central chemoreceptors in the brainstem.
2001,
Pubmed
Kofuji,
Genetic inactivation of an inwardly rectifying potassium channel (Kir4.1 subunit) in mice: phenotypic impact in retina.
2000,
Pubmed
Konstas,
Identification of domains that control the heteromeric assembly of Kir5.1/Kir4.0 potassium channels.
2003,
Pubmed
,
Xenbase
Kusaka,
Expression and polarized distribution of an inwardly rectifying K+ channel, Kir4.1, in rat retinal pigment epithelium.
1999,
Pubmed
Li,
Disruption of glucose sensing and insulin secretion by ribozyme Kir6.2-gene targeting in insulin-secreting cells.
2004,
Pubmed
Light,
Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium channels.
2000,
Pubmed
Lin,
Protein kinase C (PKC)-induced phosphorylation of ROMK1 is essential for the surface expression of ROMK1 channels.
2002,
Pubmed
,
Xenbase
Lin,
Regulation of ATP-sensitive potassium channel function by protein kinase A-mediated phosphorylation in transfected HEK293 cells.
2000,
Pubmed
Lopes,
Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
2002,
Pubmed
,
Xenbase
Mao,
Molecular basis for the inhibition of G protein-coupled inward rectifier K(+) channels by protein kinase C.
2004,
Pubmed
,
Xenbase
Pessia,
Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1.
2001,
Pubmed
,
Xenbase
Richerson,
Serotonergic neurons as carbon dioxide sensors that maintain pH homeostasis.
2004,
Pubmed
Sterling,
Inhibition of protein-tyrosine phosphatase stimulates the dynamin-dependent endocytosis of ROMK1.
2002,
Pubmed
Stevens,
Bombesin receptors inhibit G protein-coupled inwardly rectifying K+ channels expressed in Xenopus oocytes through a protein kinase C-dependent pathway.
1999,
Pubmed
,
Xenbase
Tanemoto,
In vivo formation of a proton-sensitive K+ channel by heteromeric subunit assembly of Kir5.1 with Kir4.1.
2000,
Pubmed
Tanemoto,
PDZ binding motif-dependent localization of K+ channel on the basolateral side in distal tubules.
2004,
Pubmed
Tucker,
pH dependence of the inwardly rectifying potassium channel, Kir5.1, and localization in renal tubular epithelia.
2000,
Pubmed
Vorobiov,
Agonist-independent inactivation and agonist-induced desensitization of the G protein-activated K+ channel (GIRK) in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Wang,
Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects.
2006,
Pubmed
Wang,
Regulation of ROMK channels by protein tyrosine kinase and tyrosine phosphatase.
2002,
Pubmed
Wischmeyer,
Receptor stimulation causes slow inhibition of IRK1 inwardly rectifying K+ channels by direct protein kinase A-mediated phosphorylation.
1996,
Pubmed
Wu,
Allosteric modulation of the mouse Kir6.2 channel by intracellular H+ and ATP.
2002,
Pubmed
,
Xenbase
Wu,
Expression and coexpression of CO2-sensitive Kir channels in brainstem neurons of rats.
2004,
Pubmed
,
Xenbase
Xu,
A single residue contributes to the difference between Kir4.1 and Kir1.1 channels in pH sensitivity, rectification and single channel conductance.
2000,
Pubmed
,
Xenbase
Xu,
Molecular determinants for the distinct pH sensitivity of Kir1.1 and Kir4.1 channels.
2000,
Pubmed
,
Xenbase
Xu,
Modulation of kir4.1 and kir5.1 by hypercapnia and intracellular acidosis.
2000,
Pubmed
,
Xenbase
Yang,
Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH.
2000,
Pubmed
,
Xenbase
Zeng,
Evidence for endocytosis of ROMK potassium channel via clathrin-coated vesicles.
2002,
Pubmed
,
Xenbase
Zhang,
Mechanosensitivity of GIRK channels is mediated by protein kinase C-dependent channel-phosphatidylinositol 4,5-bisphosphate interaction.
2004,
Pubmed
,
Xenbase
Zhu,
Identification of endogenous outward currents in the human embryonic kidney (HEK 293) cell line.
1998,
Pubmed
Zhu,
Suppression of Kir2.3 activity by protein kinase C phosphorylation of the channel protein at threonine 53.
1999,
Pubmed
,
Xenbase
Zitron,
Human cardiac inwardly rectifying current IKir2.2 is upregulated by activation of protein kinase A.
2004,
Pubmed
,
Xenbase
