A MEMBRANE-ASSOCIATED COMPLEX CONTAINING THE VPS15 PROTEIN-KINASE AND THE VPS34 PI 3-KINASE IS ESSENTIAL FOR PROTEIN SORTING TO THE YEAST LYSOSOME-LIKE VACUOLE
A MEMBRANE-ASSOCIATED COMPLEX CONTAINING THE VPS15 PROTEIN-KINASE AND THE VPS34 PI 3-KINASE IS ESSENTIAL FOR PROTEIN SORTING TO THE YEAST LYSOSOME-LIKE VACUOLE
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DOI：
10.1002/j.1460-2075.1993.tb05867.x
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发表时间：
1993-05-01
期刊：
影响因子：
11.4
通讯作者：
EMR, SD
中科院分区：
文献类型：
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作者：
STACK, JH;HERMAN, PK;EMR, SD
Vps 15蛋白激酶和Vps 34磷脂酰肌醇3-激酶（PI 3-激酶）是将可溶性水解酶分选到酵母液泡所必需的。Vps 34 p的过度产生抑制与vps 15激酶结构域突变体相关的生长和空泡蛋白分选缺陷，表明Vps 15 p和Vps 34 p在功能上相互作用。亚细胞分级分离和蔗糖密度梯度表明，Vps 15 p是负责与细胞内膜组分的关联Vps 34 p。化学交联和天然免疫沉淀实验表明，Vps 15 p和Vps 34 p作为异源寡聚蛋白复合物的组分相互作用。此外，我们表明，一个完整的Vps 15蛋白激酶结构域所需的Vps 34 PI 3-激酶的激活，这表明Vps 34脂质激酶是由Vps 15 p介导的蛋白磷酸化事件。我们建议，Vps 15 p和Vps 34 p功能作为一个膜相关的信号转导复合物，调节细胞内蛋白质运输的决定，通过和脂质磷酸化事件的组件。
The Vps15 protein kinase and the Vps34 phosphatidylinositol 3-kinase (PI 3-kinase) are required for the sorting of soluble hydrolases to the yeast vacuole. Overproduction of Vps34p suppresses the growth and vacuolar protein sorting defects associated with vps15 kinase domain mutants, suggesting that Vps15p and Vps34p functionally interact. Subcellular fractionation and sucrose density gradients indicate that Vps15p is responsible for the association of Vps34p with an intracellular membrane fraction. Chemical cross-linking and native immunoprecipitation experiments demonstrate that Vps15p and Vps34p interact as components of a hetero-oligomeric protein complex. In addition, we show that an intact Vps15 protein kinase domain is required for activation of the Vps34 PI 3-kinase, suggesting that the Vps34 lipid kinase is regulated by a Vps15p-mediated protein phosphorylation event. We propose that Vps15p and Vps34p function together as components of a membrane-associated signal transduction complex that regulates intracellular protein trafficking decisions through and lipid phosphorylation events.