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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

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

Revista

Título: Biochimica et Biophysica Acta - Molecular Cell Research

Vol. 1783 Nº 7

Páginas: 1884-1892

ISSN: 0167-4889

Editora: Elsevier

Indexação

ISI Web of Knowledge - 10 Citações

Scopus - 10 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9