MPS-1 is a K+ channel beta-subunit and a serine/threonine kinase.
We report the first example of a K+ channel beta-subunit that is also a serine/threonine kinase. MPS-1 is a single-transmembrane domain protein that coassembles with voltage-gated K+ channel KVS-1 in the nervous system of the nematode Caenorhabditis elegans. Biochemical analysis shows that MPS-1 can phosphorylate KVS-1 and other substrates. Electrophysiological analysis in Chinese hamster ovary (CHO) cells demonstrates that MPS-1 activity leads to a significant decrease in the macroscopic current. Single-channel analysis and biotinylation assays indicate that MPS-1 reduces the macroscopic current by lowering the open probability of the channel. These data are consistent with a model that predicts that the MPS-1-dependent phosphorylation of KVS-1 sustains cell excitability by controlling K+ flux.
Cai
Shi-Qing
SQ
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Department of Physiology and Biophysics, 683 Hoes Lane, Piscataway, New Jersey 08854, USA.
Hernandez
Leonardo
L
Wang
Yi
Y
Park
Ki Ho
KH
Sesti
Federico
F
D020816:Amino Acid Motifs / Q000235:genetics / Q000502:physiology; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D016466:CHO Cells; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular / Q000379:methods; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D004676:Myelin Basic Protein / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D010766:Phosphorylation; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011336:Probability; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits; D012694:Serine; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods
D029742:Caenorhabditis elegans Proteins; D004791:Enzyme Inhibitors; C473893:MPS-1 protein, C elegans; D004676:Myelin Basic Protein; D015221:Potassium Channels; D021122:Protein Subunits; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D019311:Staurosporine