Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis
Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis
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DOI：
10.1016/s0092-8674(00)80982-4
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发表时间：
1996-01-26
期刊：
影响因子：
64.5
通讯作者：
Riezman, H
中科院分区：
文献类型：
--
作者：
Hicke, L;Riezman, H
α因子与Ste2p（一种G蛋白偶联的质膜受体）结合，激活一个信号转导通路并刺激受体 - 配体复合物的内吞作用。配体结合也诱导Ste2p胞质尾区的泛素化。蛋白质泛素化是Ste2p受刺激的内吞作用所必需的，因为在缺乏多种泛素结合酶的ubc突变体中，内化速度慢5到15倍。在一种C末端截短形式的Ste2p中，它在配体结合时迅速被泛素化和内吞，其胞质尾区的一个赖氨酸被精氨酸替代后，泛素化和内化作用都消失了。因此，Ste2p自身的泛素化是配体刺激的内吞作用所必需的。我们提出，泛素化介导受体 - 配体复合物的降解，不是通过蛋白酶体，而是作为内吞作用的一个信号，导致随后在溶酶体/液泡中降解。
Binding of alpha factor to Ste2p, a G protein-coupled plasma membrane receptor, activates a signal transduction pathway and stimulates endocytosis of the receptor-ligand complex. Ligand binding also induces ubiquitination of the Ste2p cytoplasmic tail. Protein ubiquitination is required for stimulated endocytosis of Steep, as internalization is 5- to 15-fold slower in ubc mutants that lack multiple ubiquitin-conjugating enzymes. In a C-terminal truncated form of Ste2p that is rapidly ubiquitinated and endocytosed in response to ligand binding, a single lysine to arginine substitution in its cytoplasmic tail eliminates both ubiquitination and internalization. Thus, ubiquitination of Ste2p itself is required for ligand-stimulated endocytosis. We propose that ubiquitination mediates degradation of receptor-ligand complexes, not via the proteasome, but by acting as a signal for endocytosis leading to subsequent degradation in the lysosome/vacuole.