The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel.
Tyrosine kinases activated by G protein-coupled receptors can phosphorylate and thereby suppress the activity of the delayed rectifier potassium channel Kv1.2. Using a yeast two-hybrid screen, we identified the small GTP-binding protein RhoA as a necessary component in this process. Coimmunoprecipitation experiments confirmed that RhoA associates with Kv1.2. Electrophysiological analyses revealed that overexpression of RhoA markedly reduced the basal current generated by Kv1.2 expressed in Xenopus oocytes. Furthermore, in 293 cells expressing Kv1.2 and ml muscarinic acetylcholine receptors, inactivating RhoA using C3 exoenzyme blocked the ability of ml receptors to suppress Kv1.2 current. Therefore, these results demonstrate that RhoA regulates Kv1.2 activity and is a central component in the mechanism of receptor-mediated tyrosine kinase-dependent suppression of Kv1.2.
Cachero
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Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Morielli
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Peralta
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D036002:ADP Ribose Transferases; D000818:Animals; D001905:Botulinum Toxins; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005910:Glioma; D006801:Humans; D051663:Kv1.2 Potassium Channel; D018721:Muscarinic Agonists / Q000494:pharmacology; D009865:Oocytes; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011976:Receptors, Muscarinic; D011993:Recombinant Fusion Proteins; D019789:Tetraethylammonium / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology; D014982:Xenopus laevis; D020742:rhoA GTP-Binding Protein
D004791:Enzyme Inhibitors; C496969:KCNA2 protein, human; D051663:Kv1.2 Potassium Channel; D018721:Muscarinic Agonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011976:Receptors, Muscarinic; D011993:Recombinant Fusion Proteins; D014638:Vanadates; D019789:Tetraethylammonium; D002217:Carbachol; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein