Regulation of human cardiac KCNQ1/KCNE1 channel by epidermal growth factor receptor kinase.
The aim of the present study was to investigate whether/how the recombinant human cardiac I(Ks) could be regulated by epidermal growth factor receptor kinase in HEK 293 cells stably expressing hKCNQ1/hKCNE1 genes using the approaches of perforated patch clamp technique, immunoprecipitation and Western blot analysis. It was found that the broad spectrum isoflavone tyrosine kinase inhibitor genistein and the selective epidermal growth factor receptor kinase inhibitor tyrphostin AG556 suppressed the recombinant I(Ks), and their inhibition was countered by the protein tyrosine phosphatase inhibitor orthovanadate. The Src-family kinase inhibitor PP2 reduced the current, but the effect was not antagonized by orthovanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hKCNQ1 protein was decreased by genistein or AG556, but not by PP2. These results provide the novel information that epidermal growth factor receptor kinase, but not Src-family kinases, regulates the recombinant cardiac I(Ks) stably expressed in HEK 293 cells via phosphorylating KCNQ1 protein of the channel.
Dong
Ming-Qing
MQ
Department of Medicine and Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Sun
Hai-Ying
HY
Tang
Qiang
Q
Tse
Hung-Fat
HF
Lau
Chu-Pak
CP
Li
Gui-Rong
GR
D000818:Animals; D002460:Cell Line; D004594:Electrophysiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019833:Genistein / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000378:metabolism; D014638:Vanadates / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
D051657:KCNQ1 Potassium Channel; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D020032:Tyrphostins; C098981:AG 556; D014638:Vanadates; D014443:Tyrosine; D019833:Genistein; D066246:ErbB Receptors; D019061:src-Family Kinases