Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand-induced endocytosis of the epidermal growth factor receptor
Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand-induced endocytosis of the epidermal growth factor receptor
复制标题
DOI：
10.1074/jbc.m201499200
复制
发表时间：
2002-07-19
影响因子：
4.8
通讯作者：
Daaka, Y
中科院分区：
文献类型：
--
作者：
Ahn, S;Kim, J;Daaka, Y
配体激活受体的内吞作用需要动力蛋白介导的GTP水解，该过程由动力蛋白自组装调节。在这里，我们证明了动力蛋白I被c-Src磷酸化诱导其自组装并增加其GTPase活性。电子显微镜分析显示，酪氨酸磷酸化的动力蛋白I自发地自组装成大堆环。酪氨酸597在体外和培养细胞中都被鉴定为在表皮生长因子受体刺激下被磷酸化。用苯丙氨酸取代酪氨酸597会在体外削弱Src激酶诱导的Dynamin I自组装和GTP酶活性。Y597F Dynamin I在细胞中的表达减弱了激动剂驱动的表皮生长因子受体内化。因此，动力蛋白在配体诱导的信号受体内化中的作用需要c-Src介导的酪氨酸磷酸化。
Endocytosis of ligand-activated receptors requires dynamin-mediated GTP hydrolysis, which is regulated by dynamin self-assembly. Here, we demonstrate that phosphorylation of dynamin I by c-Src induces its self-assembly and increases its GTPase activity. Electron microscopic analyses reveal that tyrosine-phosphorylated dynamin I spontaneously self-assembles into large stacks of rings. Tyrosine 597 was identified as being phosphorylated both in vitro and in cultured cells following epidermal growth factor receptor stimulation. The replacement of tyrosine 597 with phenylalanine impairs Src kinase-induced dynamin I self-assembly and GTPase activity in vitro. Expression of Y597F dynamin I in cells attenuates agonist-driven epidermal growth factor receptor internalization. Thus, c-Src-mediated tyrosine phosphorylation is required for the function of dynamin in ligand-induced signaling receptor internalization.