A novel PKC-regulated mechanism controls CD44-ezrin association and directional cell motility
A novel PKC-regulated mechanism controls CD44-ezrin association and directional cell motility
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DOI：
10.1038/ncb797
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发表时间：
2002-06-01
影响因子：
21.3
通讯作者：
Isacke, CM
中科院分区：
文献类型：
--
作者：
Legg, JW;Lewis, CA;Isacke, CM
膜-细胞骨架连接复合物的动态组装和分解对于细胞迁移至关重要。在这里，我们描述了一种调节透明质酸受体 CD44 的新型磷酸化机制。在静息细胞中，CD44 在单个丝氨酸残基 Ser325 处被组成型磷酸化。蛋白激酶 C 被激活后，磷酸化的转变导致 CD44 仅在替代残基 Ser291 处被磷酸化。使用荧光寿命成像显微镜 (FLIM) 监测的荧光共振能量转移 (FRET) 和趋化性测定，我们发现 Ser291 的磷酸化在体内调节 CD44 和细胞骨架连接蛋白 ezrin 之间的相互作用，并且这种磷酸化对于 CD44 依赖性定向细胞运动至关重要。
The dynamic assembly and disassembly of membrane-cytoskeleton junctional complexes is critical in cell migration. Here we describe a novel phosphorylation mechanism that regulates the hyaluronan receptor CD44. In resting cells, CD44 is constitutively phosphorylated at a single serine residue, Ser325. After protein kinase C is activated, a switch in phosphorylation results in CD44 being phosphorylated solely at an alternative residue, Ser291. Using fluorescence resonance energy transfer (FRET) monitored by fluorescence lifetime imaging microscopy (FLIM) and chemotaxis assays we show that phosphorylation of Ser291 modulates the interaction between CD44 and the cytoskeletal linker protein ezrin in vivo, and that this phosphorylation is critical for CD44-dependent directional cell motility.