title: Protein kinase CK2 is coassembled with small conductance Ca(2+)-activated K+ channels and regulates channel gating.
abstract: Small conductance Ca(2+)-activated K+ channels (SK channels) couple the membrane potential to fluctuations in intracellular Ca2+ concentration in many types of cells. SK channels are gated by Ca2+ ions via calmodulin that is constitutively bound to the intracellular C terminus of the channels and serves as the Ca2+ sensor. Here we show that, in addition, the cytoplasmic N and C termini of the channel protein form a polyprotein complex with the catalytic and regulatory subunits of protein kinase CK2 and protein phosphatase 2A. Within this complex, CK2 phosphorylates calmodulin at threonine 80, reducing by 5-fold the apparent Ca2+ sensitivity and accelerating channel deactivation. The results show that native SK channels are polyprotein complexes and demonstrate that the balance between kinase and phosphatase activities within the protein complex shapes the hyperpolarizing response mediated by SK channels.
authors.affiliation: Complexio GmbH Labor, Hermann-Herder-Str. 7, 79104 Freiburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bildl
authors.forename: Tim
authors.initials: T
authors.lastname: Strassmaier
authors.forename: Henrike
authors.initials: H
authors.lastname: Thurm
authors.forename: Jens
authors.initials: J
authors.lastname: Andersen
authors.forename: Silke
authors.initials: S
authors.lastname: Eble
authors.forename: Dominik
authors.initials: D
authors.lastname: Oliver
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Uwe
authors.initials: U
authors.lastname: Schulte
authors.forename: John P
authors.initials: JP
authors.lastname: Adelman
authors.forename: Bernd
authors.initials: B
authors.lastname: Fakler
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D047390:Casein Kinase II; D002462:Cell Membrane / Q000378:metabolism; D002846:Chromatography, Affinity / Q000379:methods; D003051:Cochlea / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D015640:Ion Channel Gating / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology; D013058:Mass Spectrometry / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal / Q000379:methods; D016296:Mutagenesis / Q000502:physiology; D009154:Mutation; D033661:Oocysts; D018408:Patch-Clamp Techniques / Q000379:methods; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D015221:Potassium Channels / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D011485:Protein Binding; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels; D013096:Spermine / Q000494:pharmacology; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D020798:Two-Hybrid System Techniques; D014981:Xenopus
chemical_list: D002147:Calmodulin; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D021122:Protein Subunits; D051640:Small-Conductance Calcium-Activated Potassium Channels; D016708:Synaptophysin; D013096:Spermine; D000255:Adenosine Triphosphate; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D008274:Magnesium; D002118:Calcium