C-terminal threonine phosphorylation activates ERM proteins to link the cell's cortical lipid bilayer to the cytoskeleton
C-terminal threonine phosphorylation activates ERM proteins to link the cell's cortical lipid bilayer to the cytoskeleton
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DOI：
10.1006/bbrc.1998.9823
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发表时间：
1998-12-30
影响因子：
3.1
通讯作者：
Elias, L
中科院分区：
文献类型：
--
作者：
Simons, PC;Pietromonaco, SF;Elias, L
质膜由脂质双层组成，其中完整的膜蛋白通过与皮质肌动蛋白细胞骨架的调节连接而稳定。这种调节对于细胞改变形状或迁移是必要的。 ERM（ezrin-radixin-moesin）蛋白被认为提供了这种连接，其 N 端半部直接或间接通过 EBP50（ERM 结合磷蛋白，50 kDa）等接头分子与整合膜蛋白关联，而其 C 端半部与 F-肌动蛋白关联。然而，分离的 ERM 蛋白很大程度上依靠氨基端和羧基端结构域之间的分子内相互作用以休眠状态存在，从而掩盖了膜和细胞骨架关联位点，已发现根素片段的 C 端苏氨酸磷酸化会破坏其结合氨基端结构域的能力，而不影响 C 端 F-肌动蛋白结合位点。在这里，我们展示了蛋白激酶 C-theta 对全长休眠埃兹蛋白和 moesin 的 C 端磷酸化，同时揭示了 F-肌动蛋白和 EBP50 结合位点。细胞中moesin磷酸化的增加与moesin与皮质肌动蛋白细胞骨架的关联性增加相关。这些结果表明，ERM 蛋白的激活可以通过单个 C 末端苏氨酸残基的磷酸化来完成。 (C) 1998 年学术出版社。
The plasma membrane consists of a lipid bilayer with integral membrane proteins stabilized by regulated linkages to the cortical actin cytoskeleton. The regulation is necessary for cells to change shape ormigrate. The ERM (ezrin-radixin-moesin) proteins are believed to provide such links, with the N-terminal halves associating with integral membrane proteins, either directly or indirectly through adapter molecules like EBP50 (ERM binding phosphoprotein, 50 kDa), and their C-terminal halves associating with F-actin. However, isolated ERM proteins largely exist in a dormant state by virtue of an intramolecular interaction between amino- and carboxyl-terminal domains, thereby masking membrane and cytoskeletal association sites, C-terminal threonine phosphorylation of a fragment of radixin has been found to destroy its ability to bind the amino-terminal domain without affecting the C-terminal F-actin binding site. Here we show that C-terminal phosphorylation of full-length, dormant ezrin and moesin by protein kinase C-theta simultaneously unmasks both the F-actin and EBP50 binding sites. Increased phosphorylation of moesin in cells correlated with increased association of moesin with the cortical actin cytoskeleton. These results show that activation of ERM proteins can be accomplished by phosphorylation of a single C-terminal threonine residue. (C) 1998 Academic Press.