Two new members of a family of Ypt/Rab GTPase activating proteins - Promiscuity of substrate recognition
Two new members of a family of Ypt/Rab GTPase activating proteins - Promiscuity of substrate recognition
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DOI：
10.1074/jbc.274.47.33186
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发表时间：
1999-11-19
影响因子：
4.8
通讯作者：
Gallwitz, D
中科院分区：
文献类型：
--
作者：
Albert, S;Gallwitz, D
Ras 超家族的单体 GTP 酶具有非常缓慢的内在 GTP 酶活性，特定的 GTP 酶激活蛋白可加速该活性。与已进行详细研究的 Ras 和 Rho 特异性 GTP 酶激活蛋白 (GAP) 相比，我们对 Ypt/Rab 转运 GTP 酶特异性 GAP 的功能知之甚少。我们已经鉴定了两个新的 Ypt/Rab-GAP，因为它们与三个已知的 GAP Gyp1p、Gyp6p 和 Gyp7p 的序列相关性。 Mdr1/Gyp2p 是 Ypt6p 和 Sec4p 的有效 GAP，而 Msb3/Gyp3p 是 Sec4p、Ypt6p、Ypt51p、Ypt31/Ypt32p 和 Ypt1p 的有效 GAP。尽管Msb3/Gyp3p与其首选底物Sec4p的亲和力较低(K-m = 154 mu M)，但它加速了Sec4p的内在GTPase活性5 x 10(5)倍。 Msb3/Gyp3p 似乎在功能上与 Cdc42p 调节途径相关。结果表明，酵母中有一个大家族的 Ypt/Rab-GAP，其成员在参与调节外吞和内吞运输途径不同步骤的 GTP 酶之间的区分效果很差。
Monomeric GTPases of the Ras superfamily have a very slow intrinsic GTPase activity which is accelerated by specific GTPase-activating proteins. In contrast to Ras- and Rho-specific GTPase-activating proteins (GAPs) that have been studied in great detail, little is known about the functioning of GAPs specific for Ypt/Rab transport GTPases. We have identified two novel Ypt/Rab-GAPs because of their sequence relatedness to the three known GAPs Gyp1p, Gyp6p, and Gyp7p. Mdr1/Gyp2p is an efficient GAP for Ypt6p and Sec4p, whereas Msb3/Gyp3p is a potent GAP for Sec4p, Ypt6p, Ypt51p, Ypt31/Ypt32p, and Ypt1p. Although the affinity of Msb3/Gyp3p for its preferred substrate Sec4p is low (K-m = 154 mu M), it accelerates the intrinsic GTPase activity of Sec4p 5 x 10(5)-fold. Msb3/Gyp3p appears to be functionally linked to Cdc42p-regulated pathway(s). The results demonstrate that in yeast there is a large family of Ypt/Rab-GAPs, members of which discriminate poorly between GTPases involved in regulating different steps of exo- and endocytic transport routes.