Cross-talk between G-protein and protein kinase C modulation of N-type calcium channels is dependent on the G-protein β subunit isoform
Cross-talk between G-protein and protein kinase C modulation of N-type calcium channels is dependent on the G-protein β subunit isoform
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DOI：
10.1074/jbc.c000673200
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发表时间：
2000-12-29
影响因子：
4.8
通讯作者：
Zamponi, GW
中科院分区：
文献类型：
--
作者：
Cooper, CB;Arnot, MI;Zamponi, GW
蛋白激酶和 G 蛋白对 N 型钙电流的调节是微调神经递质释放的一个因素。我们之前已经证明，α (1B) 钙通道结构域 I-II 接头区域中苏氨酸 422 的磷酸化导致生长抑素受体介导的通道 G 蛋白抑制显着减少，并且 I-II 接头因此充当蛋白激酶 C (PKC) 和 G 蛋白之间串扰的整合中心 (Hamid, J,, Nelson, D,, Spaetgens, R,, Dubel, S, J,, Snutch, T. P, 和 Zamponi, G, W, (1999) J, Biol, Chem, 274, 6195-6202)，这里我们表明，与生长抑素受体相比，阿片受体介导的 N 型通道抑制受到的影响程度较小，暗示了这种可能性 PKC/G 蛋白串扰可能取决于 G 蛋白亚型。为了解决这个问题，我们检查了四种不同类型的 G 蛋白 β 亚基对野生型和突变型 α (1B) 钙通道的影响，其中残基 422 已被谷氨酸取代以模拟 PKC 依赖性磷酸化，以及对被蛋白激酶 C 直接磷酸化的通道的影响。我们的数据表明，残基 422 的磷酸化或突变会拮抗该效应 G beta (1) 对通道活性的影响，而 G beta (2)、G beta (3) 和 G beta (4) 不受影响。因此，我们的数据表明，观察到的 G 蛋白和 N 型通道的蛋白激酶 C 调节之间的串扰是 G beta (1) 亚基的选择性特征。
The modulation of N-type calcium current by protein kinases and G-proteins is a factor in the fine tuning of neurotransmitter release. We have previously shown that phosphorylation of threonine 422 in the alpha (1B) calcium channel domain I-II linker region resulted in a dramatic reduction in somatostatin receptor-mediated G-protein inhibition of the channels and that the I-II linker consequently serves as an integration center for cross-talk between protein kinase C (PKC) and G-proteins (Hamid, J,, Nelson, D,, Spaetgens, R,, Dubel, S, J,, Snutch, T. P,, and Zamponi, G, W, (1999) J, Biol, Chem, 274, 6195-6202), Here we show that opioid receptor-mediated inhibition of N-type channels is affected to a lesser extent compared with that seen with somatostatin receptors, hinting at the possibility that PKC/G-protein cross-talk might be dependent on the G-protein subtype. To address this issue, we have examined the effects of four different types of G-protein beta subunits on both wild type and mutant alpha (1B) calcium channels in which residue 422 has been replaced by glutamate to mimic PKC-dependent phosphorylation and on channels that have been directly phosphorylated by protein kinase C, Our data show that phosphorylation or mutation of residue 422 antagonizes the effect of G beta (1) on channel activity, whereas G beta (2) G beta (3), and G beta (4) are not affected. Our data therefore suggest that the observed cross-talk between G-proteins and protein kinase C modulation of N-type channels is a selective feature of the G beta (1) subunit.