ASSOCIATION OF SRC TYROSINE KINASE WITH A HUMAN POTASSIUM CHANNEL MEDIATED BY SH3 DOMAIN

The human Kv1.5 potassium channel (hKv1.5) contains proline-rich seque nces identical to those that bind to src homology 3 (SH3) domains. Dir ect association of the Src tyrosine kinase with cloned hKv1.5 and nati ve hKv1.5 in human myocardium was observed. This interaction was media ted by the proline-rich motif of hKv1.5 and the SH3 domain of Src. Fur thermore, hKv1.5 was tyrosine phosphorylated, and the channel current was suppressed, in cells coexpressing v-Src. These results provide dir ect biochemical evidence for a signaling complex composed of a potassi um channel and a protein tyrosine kinase.