Phosphorylation-Dependent and Phosphorylation-Independent Modes of Modulation of Shaker Family Voltage-Gated Potassium Channels by Src Family Protein Tyrosine Kinases
Phosphorylation-Dependent and Phosphorylation-Independent Modes of Modulation of Shaker Family Voltage-Gated Potassium Channels by Src Family Protein Tyrosine Kinases
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Src 家族蛋白酪氨酸激酶对 Shaker 家族电压门控钾通道的磷酸化依赖性和磷酸化非依赖性调节模式
作者：
M. Nitabach;D. Llamas;I. Thompson;Kerry A Collins;T. Holmes
通过蛋白磷酸化调节电压门控钾（Kv）通道在调节细胞膜性质中起重要作用。蛋白质-蛋白质结合结构域，如Src同源3（SH 3）结构域，通过将通道与细胞内信号传导酶偶联来指导离子通道调节。传统观点认为，蛋白激酶与离子通道的结合通过使通道底物与酶物理接近而导致调节，从而促进通道的共价修饰。Src家族蛋白酪氨酸激酶（PTKs）对Kv1.5电流的SH 3结构域结合依赖性功能抑制被认为是这种机制的典型例子。在本研究中，我们解决是否SH 3依赖性结合Src家族PTKs toShaker家族Kvs介导的调节事件是独立的和/或依赖于Src催化的酪氨酸磷酸化的通道。我们发现Src结合和酪氨酸磷酸化都能够独立地调节Kv 1家族的宏观通道电流。Src的SH 3依赖性结合导致抑制Kv1.5和Kv1.4（修改为含有富含脯氨酸的SH 3结构域结合位点）宏观电流，即使在没有Src催化的酪氨酸磷酸化，而结合独立的酪氨酸磷酸化Src导致抑制Kv1.5宏观电流和Kv1.4失活动力学的调制。
Modulation of voltage-gated potassium (Kv) channels by protein phosphorylation plays an essential role in the regulation of the membrane properties of cells. Protein–protein binding domains, such as Src homology 3 (SH3) domains, direct ion channel modulation by coupling the channels with intracellular signaling enzymes. The conventional view is that protein kinase binding to ion channels leads to modulation by bringing the channel substrate into physical proximity to the enzyme, thereby fostering covalent modification of the channel. The SH3 domain binding-dependent functional suppression of Kv1.5 currents by Src family protein tyrosine kinases (PTKs) is considered a canonical example of this type of mechanism. In the present study we address whether the SH3-dependent binding of Src family PTKs toShaker family Kvs mediates modulatory events that are independent of and/or dependent on Src-catalyzed tyrosine phosphorylation of the channel. We find that Src binding and tyrosine phosphorylation are each able to modulate Kv1 family macroscopic channel currents independently. SH3-dependent binding of Src leads to the suppression of both Kv1.5 and Kv1.4 (modified to contain proline-rich SH3 domain binding sites) macroscopic currents even in the absence of Src-catalyzed tyrosine phosphorylation, whereas binding-independent tyrosine phosphorylation by Src leads to the suppression of Kv1.5 macroscopic currents and the modulation of Kv1.4 inactivation kinetics.
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影响因子：
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作者：
A. L. Goldin
通讯作者：
A. L. Goldin
影响因子：
11.4
作者：
RICKLES, RJ;BOTFIELD, MC;ZOLLER, MJ
通讯作者：
ZOLLER, MJ
Src 的 SH3 结构域的缺失会干扰磷酸化羧基末端酪氨酸的调节。
DOI：
--
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Okada,M;Howell,BW;Broome,MA;Cooper,JA
通讯作者：
Cooper,JA
激素诱导 Kv1.5 基因表达后，K 通道亚基组成发生改变。
DOI：
10.1021/bi961290s
发表时间：
1996
期刊：
Biochemistry.
影响因子：
--
作者：
Takimoto,K;Levitan,ES
通讯作者：
Levitan,ES
蛋白激酶 C 对失活的人心脏 K 通道的调节。
影响因子：
20.1
作者：
Murray,KT;Fahrig,SA;Deal,KK;Po,SS;Hu,NN;Snyders,DJ;Tamkun,MM;Bennett,PB
通讯作者：
Bennett,PB