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 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.
Holmes
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TC
Department of Biochemistry and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02254, USA.
Fadool
D A
DA
Ren
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R
Levitan
I B
IB
D000595:Amino Acid Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D051666:Kv1.5 Potassium Channel; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D018909:src Homology Domains / Q000502:physiology*; D019061:src-Family Kinases / Q000737:chemistry / Q000378:metabolism*
C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D015688:Oncogene Protein pp60(v-src); D019061:src-Family Kinases