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Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain
T C Holmes1, D A Fadool, R Ren
1Department of Biochemistry and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02254, USA.
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.