Association of Src Tyrosine Kinase with a Human Potassium Channel Mediated by SH3 Domain
Todd C. Holmes, Debra Ann Fadool, Ruibao Ren, Irwin B. Levitan
Abstract
Todd C. Holmes, Debra Ann Fadool, Ruibao Ren, Irwin B. Levitan
Abstract
The human Kv1.5 potassium channel (hKv1.5) contains proline-rich sequences identical to those that bind to Src homology 3 (SH3) domains. Direct association of the Src tyrosine kinase with cloned hKv1.5 and native hKv1.5 in human myocardium was observed. This interaction was mediated by the proline-rich motif of hKv1.5 and the SH3 domain of Src. Furthermore, hKv1.5 was tyrosine phosphorylated, and the channel current was suppressed, in cells coexpressing v-Src. These results provide direct biochemical evidence for a signaling complex composed of a potassium channel and a protein tyrosine kinase.
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The human Kv1.5 potassium channel (hKv1.5) contains proline-rich sequences identical to those that bind to Src homology 3 (SH3) domains. Direct association of the Src tyrosine kinase with cloned hKv1.5 and native hKv1.5 in human myocardium was observed. This interaction was mediated by the proline-rich motif of hKv1.5 and the SH3 domain of Src. Furthermore, hKv1.5 was tyrosine phosphorylated, and the channel current was suppressed, in cells coexpressing v-Src. These results provide direct biochemical evidence for a signaling complex composed of a potassium channel and a protein tyrosine kinase.
Key concepts: SH3 domain, Proto-oncogene tyrosine-protein kinase Src, SH2 domain, Tyrosine kinase, Tyrosine-protein kinase CSK, Tyrosine, Potassium channel, Cell biology