Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex

Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex
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DOI:
10.1126/science.285.5424.93
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发表时间:
1999-07-02
期刊:
影响因子:
56.9
通讯作者:
Scott, JD
Scott, JD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Westphal, RS;Tavalin, SJ;Scott, JD

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激酶和磷酸酶对 N-甲基-D-天冬氨酸 (NMDA) 受体活性的调节有助于突触传递的调节。建议将这些酶靶向底物附近以增强磷酸化依赖性调节。 Yotiao 是一种 NMDA 受体相关蛋白,可结合 I 型蛋白磷酸酶 (PP1) 和腺苷 3',5'-单磷酸 (cAMP) 依赖性蛋白激酶 (PKA) 全酶。锚定的 PP1 具有活性,限制通道活性,而 PKA 激活克服了 PP1 的固有活性,并导致 NMDA 受体电流快速增强。因此,yotiao 是一种支架蛋白,可将 PP1 和 PKA 物理连接至 NMDA 受体以调节通道活性。
Regulation of N-methyl-D-aspartate (NMDA) receptor activity by kinases and phosphatases contributes to the modulation of synaptic transmission. Targeting of these enzymes near the substrate is proposed to enhance phosphorylation-dependent modulation. Yotiao, an NMDA receptor-associated protein, bound the type I protein phosphatase (PP1) and the adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) holoenzyme. Anchored PP1 was active, limiting channel activity, whereas PKA activation overcame constitutive PP1 activity and conferred rapid enhancement of NMDA receptor currents. Hence, yotiao is a scaffold protein that physically attaches PP1 and PKA to NMDA receptors to regulate channel activity.