Sphingoid base signaling via Pkh kinases is required for endocytosis in yeast
Sphingoid base signaling via Pkh kinases is required for endocytosis in yeast
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DOI：
10.1093/emboj/20.23.6783
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发表时间：
2001-12-03
期刊：
影响因子：
11.4
通讯作者：
Riezman, H
中科院分区：
文献类型：
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作者：
Friant, S;Lombardi, R;Riezman, H
在酵母中，类鞘氨醇碱的合成是内吞作用的内化步骤和肌动蛋白细胞骨架的组织所必需的。我们发现，过表达的两种激酶Pkh 1 p或Pkh 2 p，这是同源的哺乳动物3-磷酸肌醇依赖性激酶-1（PDK 1），可以特异性地抑制鞘氨醇碱的合成要求的内吞作用。Pkh 1 p和Pkh 2 p具有重叠的功能，因为只有两种激酶功能受损的突变体才有内吞作用缺陷。pkh 1/2 p激酶在体外被纳摩尔浓度的鞘氨醇碱激活。这些结果表明，Pkh 1/2 p激酶是鞘氨醇碱介导的信号通路的一部分，这是所需的内吞作用的内化步骤。Pkc 1 p激酶被Pkh 1/2 p激酶磷酸化并在胞吞作用中起作用，被鉴定为该信号级联的下游效应子之一。
In yeast, sphingoid base synthesis is required for the internalization step of endocytosis and organization of the actin cytoskeleton. We show that overexpression of either one of the two kinases Pkh1p or Pkh2p, that are homologous to mammalian 3-phosphoinositide-dependent kinase-1 (PDK1), can specifically suppress the sphingoid base synthesis requirement for endocytosis. Pkh1p and Pkh2p have an overlapping function because only a mutant with impaired function of both kinases is defective for endocytosis. Pkh1/2p kinases are activated in vitro by nanomolar concentrations of sphingoid base. These results suggest that Pkh1/2p kinases are part of a sphingoid base-mediated signaling pathway that is required for the internalization step of endocytosis. The Pkc1p kinase that is phosphorylated by Pkh1/2p kinases and plays a role in endocytosis was identified as one of the downstream effectors of this signaling cascade.