Identification of a functional interaction between Kv4.3 channels and c-Src tyrosine kinase

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Pedro Gomes (Author) FMUP; Saito, T (Author) Other; del Corsso, C (Author) Other; Alioua, A (Author) Other; Eghbali, M (Author) Other; Toro, L (Author) Other; Stefani, E (Author) Other

Journal

Title: Biochimica et Biophysica Acta - Molecular Cell Research

Vol. 1783 No. 7

Pages: 1884-1892

ISSN: 0167-4889

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 10 Citations

Other information

Authenticus ID: P-003-VN5

DOI: 10.1016/j.bbamcr.2008.06.011

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9