Endocytosis as a mechanism for tyrosine kinase-dependent suppression of a voltage-gated potassium channel
Endocytosis as a mechanism for tyrosine kinase-dependent suppression of a voltage-gated potassium channel
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DOI：
10.1091/mbc.e03-11-0788
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发表时间：
2004-09-01
影响因子：
3.3
通讯作者：
Morielli, AD
中科院分区：
文献类型：
--
作者：
Nesti, E;Everill, B;Morielli, AD
电压门控钾通道Kv1.2经历酪氨酸磷酸化抑制其离子电流。然而，人们对这一过程背后的物理机制知之甚少。我们发现，Kv1.2α亚基蛋白对同样的刺激反应经历内吞作用，引起抑制Kv1.2离子电流。这个过程是酪氨酸磷酸化依赖的，因为Kv1.2 N端的相同酪氨酸到苯丙氨酸的突变赋予了对通道抑制的抵抗力(Y132F)，也赋予了对通道内吞的抵抗力。过表达显性负性动力蛋白阻断了刺激诱导的Kv1.2内吞作用，也阻断了对Kv1.2离子电流的抑制。这些数据表明，Kv1.2从细胞表面的内吞作用是酪氨酸激酶抑制通道的关键机制。
The voltage-gated potassium channel Kv1.2 undergoes tyrosine phosphorylation-dependent suppression of its ionic current. However, little is known about the physical mechanism behind that process. We have found that the Kv1.2 alpha-subunit protein undergoes endocytosis in response to the same stimuli that evoke suppression of Kv1.2 ionic current. The process is tyrosine phosphorylation-dependent because the same tyrosine to phenylalanine mutation in the N-terminus of Kv1.2 that confers resistance to channel suppression (Y132F) also confers resistance to channel endocytosis. Overexpression of a dominant negative form of dynamin blocked stimulus-induced Kv1.2 endocytosis and also blocked suppression of Kv1.2 ionic current. These data indicate that endocytosis of Kv1.2 from the cell surface is a key mechanism for channel suppression by tyrosine kinases.