Endocytosis as a mechanism for tyrosine kinase-dependent suppression of a voltage-gated potassium channel.
The voltage-gated potassium channel Kv1.2 undergoes tyrosine phosphorylation-dependent suppression of its ionic current. However, little is known about the physical mechanism behind that process. We have found that the Kv1.2 alpha-subunit protein undergoes endocytosis in response to the same stimuli that evoke suppression of Kv1.2 ionic current. The process is tyrosine phosphorylation-dependent because the same tyrosine to phenylalanine mutation in the N-terminus of Kv1.2 that confers resistance to channel suppression (Y132F) also confers resistance to channel endocytosis. Overexpression of a dominant negative form of dynamin blocked stimulus-induced Kv1.2 endocytosis and also blocked suppression of Kv1.2 ionic current. These data indicate that endocytosis of Kv1.2 from the cell surface is a key mechanism for channel suppression by tyrosine kinases.
Nesti
Edmund
E
The University of Vermont College of Medicine, Burlington, VT 05405, USA.
Everill
Brian
B
Morielli
Anthony D
AD
D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D066298:In Vitro Techniques; D051663:Kv1.2 Potassium Channel; D016297:Mutagenesis, Site-Directed; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014638:Vanadates / Q000494:pharmacology
D000911:Antibodies, Monoclonal; C496969:KCNA2 protein, human; C496972:Kcna2 protein, rat; D051663:Kv1.2 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; C076715:pervanadate; D014638:Vanadates; D002217:Carbachol; D011505:Protein-Tyrosine Kinases; D034281:Dynamins