Consensus phosphorylation sites of human GABA(C)/GABA(ρ) receptors are not critical for inhibition by protein kinase C activation

Tadashi Kusama; Kouji Hatama; Manabu Sakurai; Yasuo Kizawa; George R. Uhl; Hajime Murakami

doi:10.1016/S0304-3940(98)00696-X

Consensus phosphorylation sites of human GABA(C)/GABA(ρ) receptors are not critical for inhibition by protein kinase C activation

Tadashi Kusama, Kouji Hatama, Manabu Sakurai, Yasuo Kizawa, George R. Uhl, Hajime Murakami

School of Medicine

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

The mechanism of inhibition of human GABA(C)/GABA(ρ) receptors by protein kinase C (PKC) activation was investigated in Xenopus oocytes. Phorbol 12-myristate 13 acetate (PMA), a potent PKC activator, at 25 nM inhibited the currents through GABA(ρ2) receptors, which have one consensus phosphorylation site by PKC in the predicted intracellular loops. The time- courses and amplitudes of inhibition were not significantly different from those occurring through GABA(ρ1) receptors, which have six such sites. The inhibitory effect of PMA was also observed after removing each consensus phosphorylation site in both GABA(ρ1) and ρ2 receptors by site-directed mutagenesis. These results suggest that phosphorylation of consensus sites in the intracellular loops is not involved in the inhibition of human GABA(C)/GABA(ρ) receptors by PKC activation.

Original language	English (US)
Pages (from-to)	17-20
Number of pages	4
Journal	Neuroscience Letters
Volume	255
Issue number	1
DOIs	https://doi.org/10.1016/S0304-3940(98)00696-X
State	Published - Oct 9 1998

Keywords

ρ1 subunit
ρ2 subunit
GABA(C) receptor
Mutagenesis
Phosphorylation
Protein kinase C
Voltage clamp
Xenopus oocyte

ASJC Scopus subject areas

General Neuroscience

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10.1016/S0304-3940(98)00696-X

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title = "Consensus phosphorylation sites of human GABA(C)/GABA(ρ) receptors are not critical for inhibition by protein kinase C activation",

abstract = "The mechanism of inhibition of human GABA(C)/GABA(ρ) receptors by protein kinase C (PKC) activation was investigated in Xenopus oocytes. Phorbol 12-myristate 13 acetate (PMA), a potent PKC activator, at 25 nM inhibited the currents through GABA(ρ2) receptors, which have one consensus phosphorylation site by PKC in the predicted intracellular loops. The time- courses and amplitudes of inhibition were not significantly different from those occurring through GABA(ρ1) receptors, which have six such sites. The inhibitory effect of PMA was also observed after removing each consensus phosphorylation site in both GABA(ρ1) and ρ2 receptors by site-directed mutagenesis. These results suggest that phosphorylation of consensus sites in the intracellular loops is not involved in the inhibition of human GABA(C)/GABA(ρ) receptors by PKC activation.",

keywords = "ρ1 subunit, ρ2 subunit, GABA(C) receptor, Mutagenesis, Phosphorylation, Protein kinase C, Voltage clamp, Xenopus oocyte",

author = "Tadashi Kusama and Kouji Hatama and Manabu Sakurai and Yasuo Kizawa and Uhl, {George R.} and Hajime Murakami",

year = "1998",

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doi = "10.1016/S0304-3940(98)00696-X",

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T1 - Consensus phosphorylation sites of human GABA(C)/GABA(ρ) receptors are not critical for inhibition by protein kinase C activation

AU - Kusama, Tadashi

AU - Hatama, Kouji

AU - Sakurai, Manabu

AU - Kizawa, Yasuo

AU - Uhl, George R.

AU - Murakami, Hajime

PY - 1998/10/9

Y1 - 1998/10/9

N2 - The mechanism of inhibition of human GABA(C)/GABA(ρ) receptors by protein kinase C (PKC) activation was investigated in Xenopus oocytes. Phorbol 12-myristate 13 acetate (PMA), a potent PKC activator, at 25 nM inhibited the currents through GABA(ρ2) receptors, which have one consensus phosphorylation site by PKC in the predicted intracellular loops. The time- courses and amplitudes of inhibition were not significantly different from those occurring through GABA(ρ1) receptors, which have six such sites. The inhibitory effect of PMA was also observed after removing each consensus phosphorylation site in both GABA(ρ1) and ρ2 receptors by site-directed mutagenesis. These results suggest that phosphorylation of consensus sites in the intracellular loops is not involved in the inhibition of human GABA(C)/GABA(ρ) receptors by PKC activation.

AB - The mechanism of inhibition of human GABA(C)/GABA(ρ) receptors by protein kinase C (PKC) activation was investigated in Xenopus oocytes. Phorbol 12-myristate 13 acetate (PMA), a potent PKC activator, at 25 nM inhibited the currents through GABA(ρ2) receptors, which have one consensus phosphorylation site by PKC in the predicted intracellular loops. The time- courses and amplitudes of inhibition were not significantly different from those occurring through GABA(ρ1) receptors, which have six such sites. The inhibitory effect of PMA was also observed after removing each consensus phosphorylation site in both GABA(ρ1) and ρ2 receptors by site-directed mutagenesis. These results suggest that phosphorylation of consensus sites in the intracellular loops is not involved in the inhibition of human GABA(C)/GABA(ρ) receptors by PKC activation.

KW - ρ1 subunit

KW - ρ2 subunit

KW - GABA(C) receptor

KW - Mutagenesis

KW - Phosphorylation

KW - Protein kinase C

KW - Voltage clamp

KW - Xenopus oocyte

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DO - 10.1016/S0304-3940(98)00696-X

M3 - Article

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AN - SCOPUS:0032500785

SN - 0304-3940

VL - 255

SP - 17

EP - 20

JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 1

ER -

Consensus phosphorylation sites of human GABA(C)/GABA(ρ) receptors are not critical for inhibition by protein kinase C activation

Abstract

Keywords

ASJC Scopus subject areas

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