The conserved Pkh-Ypk kinase cascade is required for endocytosis in yeast.
The conserved Pkh-Ypk kinase cascade is required for endocytosis in yeast.
复制标题
DOI：
10.1083/jcb.200107135
复制
发表时间：
2002-01-21
期刊：
影响因子：
--
通讯作者：
Hicke L
中科院分区：
文献类型：
--
作者：
deHart AK;Schnell JD;Allen DA;Hicke L
胞吞作用激活信号受体的内化是细胞下调胞外信号的一种方式。与许多信号受体一样，酵母α-因子信息素受体在溶酶体样液泡中通过过度磷酸化、泛素化以及随后的内化和降解而下调。在检测泛素依赖性受体内化相关蛋白的筛选中，我们确定了鞘碱调节的丝氨酸-苏氨酸激酶Ypk1。Ypk1是哺乳动物血清和糖皮质激素诱导的激酶SGK的同源物，SGK可以替代Ypk1在酵母中的功能。Ypk1的激酶活性是受体内吞作用所必需的，因为对其催化活性重要的两个残基的突变导致α-因子内化的严重缺陷。Ypk1是受体介导和液相内吞作用所必需的，而不是受体磷酸化或泛素化所必需的。Ypk1本身被Pkh激酶磷酸化，Pkh激酶是哺乳动物PDK1的同源物。Ypk1中被Pkh1磷酸化的苏氨酸是有效内吞所必需的，pkh突变细胞在α-因子内化和液相内吞方面存在缺陷。这些观察结果表明，Ypk1作用于Pkh激酶的下游，通过磷酸化内吞机制的成分来控制内吞作用。
Internalization of activated signaling receptors by endocytosis is one way cells downregulate extracellular signals. Like many signaling receptors, the yeast α-factor pheromone receptor is downregulated by hyperphosphorylation, ubiquitination, and subsequent internalization and degradation in the lysosome-like vacuole. In a screen to detect proteins involved in ubiquitin-dependent receptor internalization, we identified the sphingoid base–regulated serine–threonine kinase Ypk1. Ypk1 is a homologue of the mammalian serum– and glucocorticoid-induced kinase, SGK, which can substitute for Ypk1 function in yeast. The kinase activity of Ypk1 is required for receptor endocytosis because mutations in two residues important for its catalytic activity cause a severe defect in α-factor internalization. Ypk1 is required for both receptor-mediated and fluid-phase endocytosis, and is not necessary for receptor phosphorylation or ubiquitination. Ypk1 itself is phosphorylated by Pkh kinases, homologues of mammalian PDK1. The threonine in Ypk1 that is phosphorylated by Pkh1 is required for efficient endocytosis, and pkh mutant cells are defective in α-factor internalization and fluid-phase endocytosis. These observations demonstrate that Ypk1 acts downstream of the Pkh kinases to control endocytosis by phosphorylating components of the endocytic machinery.
登录
查看更多内容
DOI：
10.1083/jcb.135.6.1789
发表时间：
1996-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Tan PK;Howard JP;Payne GS
通讯作者：
Payne GS
影响因子：
4.8
作者：
Bauerfeind, R;Takei, K;De Camilli, P
通讯作者：
De Camilli, P
影响因子：
9.2
作者：
Casamayor, A;Torrance, PD;Alessi, DR
通讯作者：
Alessi, DR
影响因子：
4.8
作者：
Li, RX;Blanchette-Mackie, EJ;Ladisch, S
通讯作者：
Ladisch, S
影响因子：
2.6
作者：
HORVATH, A;RIEZMAN, H
通讯作者：
RIEZMAN, H