Wilde A, Beattie E C, Lem L, Riethof D A, Liu S H, Mobley W C, Soriano P, Brodsky F M
Department of Immunology and Microbiology, University of California, San Francisco 94143-0552, USA.
Cell. 1999 Mar 5;96(5):677-87. doi: 10.1016/s0092-8674(00)80578-4.
Epidermal growth factor (EGF) binding to its receptor causes rapid phosphorylation of the clathrin heavy chain at tyrosine 1477, which lies in a domain controlling clathrin assembly. EGF-mediated clathrin phosphorylation is followed by clathrin redistribution to the cell periphery and is the product of downstream activation of SRC kinase by EGF receptor (EGFR) signaling. In cells lacking SRC kinase, or cells treated with a specific SRC family kinase inhibitor, EGF stimulation of clathrin phosphorylation and redistribution does not occur, and EGF endocytosis is delayed. These observations demonstrate a role for SRC kinase in modification and recruitment of clathrin during ligand-induced EGFR endocytosis and thereby define a novel effector mechanism for regulation of endocytosis by receptor signaling.
表皮生长因子（EGF）与其受体结合会导致网格蛋白重链在酪氨酸1477处快速磷酸化，该酪氨酸位于控制网格蛋白组装的结构域中。EGF介导的网格蛋白磷酸化之后是网格蛋白重新分布到细胞周边，这是EGF受体（EGFR）信号传导下游激活SRC激酶的产物。在缺乏SRC激酶的细胞或用特定SRC家族激酶抑制剂处理的细胞中，EGF刺激不会发生网格蛋白磷酸化和重新分布，并且EGF内吞作用会延迟。这些观察结果证明了SRC激酶在配体诱导的EGFR内吞过程中对网格蛋白的修饰和募集作用，从而确定了一种通过受体信号传导调节内吞作用的新型效应机制。
