IDENTIFICATION OF A SPECIFIC INS(1,3,4,5)P-4-BINDING PROTEIN AS A MEMBER OF THE GAP1 FAMILY
IDENTIFICATION OF A SPECIFIC INS(1,3,4,5)P-4-BINDING PROTEIN AS A MEMBER OF THE GAP1 FAMILY
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DOI：
10.1038/376527a0
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发表时间：
1995-08-10
期刊：
影响因子：
64.8
通讯作者：
IRVINE, RF
中科院分区：
文献类型：
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作者：
CULLEN, PJ;HSUAN, JJ;IRVINE, RF
肌醇1，3，4，5-三磷酸(Ins(1，4，5)P-3)在刺激细胞(1，2)中能快速合成1，3，4，5-四磷酸肌醇(Ins(1，3，4，5)P-4)。尽管进行了广泛的实验，但这种肌醇磷酸的细胞功能还没有明确的定义。INS(1，3，4，5)P-4的特异结合部位已经在几个组织中被鉴定(3，4)，我们已经纯化了一个这样的蛋白以获得均一(5)。它对INS(1，3，4，5)P-4的高亲和力和对这种异构体构型(5，6)的高度特异性，表明它可能是一种INS(1，3，4，5)P-4受体。在这里，我们报道了该蛋白作为GTP酶激活蛋白的克隆和特性，特别是GAP家族的一个成员。在体外，它对Rap和Ras都显示出GAP活性，但只有Ras的GAP活性被磷脂抑制，并被Ins(1，3，4，5)P-4特异性刺激。
INOSITOL 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P-4) is produced rapidly from inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) in stimulated cells(1,2). Despite extensive experimentation, no clearly defined cellular function has yet been described for this inositol phosphate. Binding sites specific for Ins(1,3,4,5)P-4 have been identified in several tissues(3,4), and we have purified one such protein to homogeneity(5). Its high affinity for Ins(1,3,4,5)P-4, and its exquisite specificity for this isomeric configuration(5,6), suggest it may be an Ins(1,3,4,5)P-4 receptor. Here we report the cloning and characterization of this protein as a GTPase-activating protein, specifically a member of the GAP family. In vitro it shows GAP activity against both Rap and Ras, but only the Ras GAP activity is inhibited by phospholipids and is specifically stimulated by Ins(1,3,4,5)P-4.