Identification of a functional interaction between Kv4.3 channels and c-Src tyrosine kinase.
Identification of a functional interaction between Kv4.3 channels and c-Src tyrosine kinase.
复制标题
鉴定 Kv4.3 通道和 c-Src 酪氨酸激酶之间的功能相互作用。
DOI：
10.1016/j.bbamcr.2008.06.011
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Stefani,Enrico
中科院分区：
文献类型：
--
作者：
Gomes,Pedro;Saito,Tomoaki;DelCorsso,Cris;Alioua,Abderrahmane;Eghbali,Mansoureh;Toro,Ligia;Stefani,Enrico
Voltage-gated K+(Kv) channels are key determinants of cardiac and neuronal excitability. A substantial body of evidence has accumulated in support of a role for Src family tyrosine kinases in the regulation of Kv channels. In this study, we examined the possibility that c-Src tyrosine kinase participates in the modulation of the transient voltage-dependent K+channel Kv4.3. Supporting a mechanistic link between Kv4.3 and c-Src, confocal microscopy analysis of HEK293 cells stably transfected with Kv4.3 showed high degree of co-localization of the two proteins at the plasma membrane. Our results further demonstrate an association between Kv4.3 and c-Src by co-immunoprecipitation and GST pull-down assays, this interaction being mediated by the SH2 and SH3 domains of c-Src. Furthermore, we show that Kv4.3 is tyrosine phosphorylated under basal conditions. The functional relevance of the observed interaction between Kv4.3 and c-Src was established in patch-clamp experiments, where application of the Src inhibitor PP2 caused a decrease in Kv4.3 peak current amplitude, but not the inactive structural analogue PP3. Conversely, intracellular application of recombinant c-Src kinase or the protein tyrosine phosphatase inhibitor bpV(phen) increased Kv4.3 peak current amplitude. In conclusion, our findings provide evidence that c-Src-induced Kv4.3 channel activation involves their association in a macromolecular complex and suggest a role for c-Src-Kv4.3 pathway in regulating cardiac and neuronal excitability.
