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. Research Abstract Details 

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

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.

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

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

PUBLICATION TYPE: Journal Article

Journal: Biochimica et biophysica acta

VOLUME: 1783

Page Numbers: 1884-92

Journal Abbreviation: Biochim. Biophys. Acta

ISSN: 0006-3002

DAY: 20

MONTH: 06

YEAR: 2008

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

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LANGUAGE: eng

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

AFFILIATION: Department of Anesthesiology, Division of Molecular Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095-1778, USA.

Country: Netherlands

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MEDLINETA: Biochim Biophys Acta

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