REGULATION OF GABA(A) RECEPTOR FUNCTION BY PROTEIN-KINASE-C PHOSPHORYLATION
REGULATION OF GABA(A) RECEPTOR FUNCTION BY PROTEIN-KINASE-C PHOSPHORYLATION
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DOI：
10.1016/0896-6273(94)90316-6
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发表时间：
1994-05-01
期刊：
影响因子：
16.2
通讯作者：
SMART, TG
中科院分区：
文献类型：
--
作者：
KRISHEK, BJ;XIE, XM;SMART, TG
GABA（A）受体具有通过PKC磷酸化的共有序列，其位于β和γ 2亚基的假定胞内结构域上。使用纯化的受体亚基分析PKC磷酸化位点，并位于β 1和γ 2亚基中的3个丝氨酸残基上。使用在肾细胞和爪蟾卵母细胞中表达的重组受体研究了磷酸化在受体功能中的作用，并与天然神经元GABA（A）受体进行了比较。对于重组和天然GABA（A）受体，PKC磷酸化引起GABA激活电流幅度的降低，而不影响电流衰减的时间常数。丝氨酸残基的选择性定点诱变降低了佛波醇酯的作用，并揭示了γ 2亚基中的丝氨酸343对GABA激活的反应产生最大的影响。这些结果表明，PKC磷酸化可以差异调节GABA（A）受体的功能。
GABA(A) receptors possess consensus sequences for phosphorylation by PKC that are located on the presumed intracellular domains of beta and gamma 2 subunits. PKC phosphorylation sites were analyzed using purified receptor subunits and were located on up to 3 serine residues in beta 1 and gamma 2 subunits. The role of phosphorylation in receptor function was studied using recombinant receptors expressed in kidney cells and Xenopus oocytes and was compared with native neuronal GABA(A) receptors. For recombinant and native GABA(A) receptors, PKC phosphorylation caused a reduction in the amplitudes of GABA-activated currents without affecting the time constants for current decay. Selective site-directed mutagenesis of the serine residues reduced the effects of phorbol esters and revealed that serine 343 in the gamma 2 subunit exerted the largest effect on the GABA-activated response. These results indicate that PKC phosphorylation can differentially modulate GABA(A) receptor function.