TYPE-I, TYPE-II, AND TYPE-III INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS ARE UNEQUALLY SUSCEPTIBLE TO DOWN-REGULATION AND ARE EXPRESSED IN MARKEDLY DIFFERENT PROPORTIONS IN DIFFERENT CELL-TYPES
TYPE-I, TYPE-II, AND TYPE-III INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS ARE UNEQUALLY SUSCEPTIBLE TO DOWN-REGULATION AND ARE EXPRESSED IN MARKEDLY DIFFERENT PROPORTIONS IN DIFFERENT CELL-TYPES
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DOI：
10.1074/jbc.270.19.11678
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发表时间：
1995-05-12
影响因子：
4.8
通讯作者：
WOJCIKIEWICZ, RJH
中科院分区：
文献类型：
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作者：
WOJCIKIEWICZ, RJH
I 型肌醇 1,4,5-三磷酸 (InsP(3)) 受体在磷酸肌醇水解的刺激过程中可以从细胞中快速耗尽，因为其降解加速（Wojcikiewicz, R. J. H., Furuichi, T., Nakade, S., Mikoshiba, K., 和 Nahorski, S. R. (1994) J. Biol. Chem. 269， 7963-7969）。本研究检查了 II 型和 III 型 InsP(3) 受体的调节特性。最初，通过定量免疫印迹确定了一系列细胞类型中 InsP(3) 受体的相对丰度。这些研究表明，I型、II型和III型InsP受体的表达比例差异很大，并且某些细胞（例如AR4-2J大鼠胰腺瘤细胞）表达所有三种受体。胆囊收缩素和铃蟾肽对 AR4-2J 细胞的影响分析表明，在磷酸肌醇水解激活过程中，每种 InsP(3) 受体均可下调，但 II 型受体的消耗有限。这种差异也出现在大鼠小脑颗粒细胞中，并且发现是由于II型受体相对不易降解所致。综上所述，I型、II型和III型受体均可以下调，但具有不同的特征。由于 InsP(3) 受体的相对丰度变化很大，下调过程的激活改变细胞内信号传导的程度将根据表达的 InsP(3) 受体而变化。
The type I inositol 1,4,5-trisphosphate (InsP(3)) receptor can be rapidly depleted from cells during stimulation of phosphoinositide hydrolysis because its degradation is accelerated (Wojcikiewicz, R. J. H., Furuichi, T., Nakade, S., Mikoshiba, K., and Nahorski, S. R. (1994) J. Biol. Chem. 269, 7963-7969). The present study examines the regulatory properties of type II and III InsP(3) receptors.Initially, the relative abundance of InsP(3) receptors was defined in a range of cell types by quantitative immunoblotting. These studies showed that the proportions in which type I, II, and III InsP, receptors are expressed differs greatly and that some cells (for example, AR4-2J rat pancreatoma cells) express all three receptors. Analysis of the effects of cholecystokinin and bombesin on AR4-2J cells showed that each of the InsP(3) receptors could be down-regulated during activation of phosphoinositide hydrolysis, but that depletion of the type II receptor was limited. Such a discrepancy was also seen in rat cerebellar granule cells and was found to result from the type II receptor being relatively resistant to degradation.In conclusion, type I, II, and III receptors can all be down-regulated, but with different characteristics. As the relative abundance of InsP, receptors is extremely variable, the extent to which activation of the down-regulatory process alters intracellular signaling will vary depending on which InsP(3) receptors are expressed.