Krishek B J, Xie X, Blackstone C, Huganir R L, Moss S J, Smart T G
Department of Pharmacology, School of Pharmacy, London, England.
Neuron. 1994 May;12(5):1081-95. doi: 10.1016/0896-6273(94)90316-6.
GABAA 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 GABAA receptors. For recombinant and native GABAA 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 GABAA receptor function.
GABAA受体具有蛋白激酶C（PKC）磷酸化的共有序列，这些序列位于β和γ2亚基假定的胞内结构域上。使用纯化的受体亚基分析PKC磷酸化位点，其位于β1和γ2亚基中多达3个丝氨酸残基上。利用在肾细胞和非洲爪蟾卵母细胞中表达的重组受体研究磷酸化在受体功能中的作用，并与天然神经元GABAA受体进行比较。对于重组和天然GABAA受体，PKC磷酸化导致GABA激活电流的幅度降低，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酯的作用，并表明γ2亚基中的丝氨酸343对GABA激活反应的影响最大。这些结果表明，PKC磷酸化可以差异性地调节GABAA受体功能。
