title: CK2 negatively regulates Galphas signaling.
abstract: We present evidence, using biochemical and cellular approaches, that the kinase, CK2, negatively controls signaling via Galpha(s) (or Galpha(olf)) coupled to dopamine D1 and adenosine A2A receptors. Pharmacological inhibition of CK2 or CK2 knockdown by RNAi lead to elevated cAMP levels in dopamine D1 receptor-activated neuroblastoma cells. Phosphorylation levels of protein kinase A substrates were increased in the presence of CK2 inhibitors in mouse striatal slices. The effect of D1 receptor and A2A receptor agonists on the phosphorylation of protein kinase A sites was potentiated upon CK2 inhibition. Furthermore, in cell lines, we observed that reduction in CK2 activity, pharmacologically or genetically, reduced the amount of D1 receptor that was internalized in response to dopamine. Finally, the beta subunit of CK2 was found to interact specifically with the Galpha(s) subunit through protein interaction analyses. Thus CK2 can inhibit G protein-coupled receptor action by enabling faster receptor internalization, possibly through a direct association with Galpha(s).
authors: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA.
authors: Heike
authors: H
authors: Rebholz
authors: Akinori
authors: A
authors: Nishi
authors: Sabine
authors: S
authors: Liebscher
authors: Angus C
authors: AC
authors: Nairn
authors: Marc
authors: M
authors: Flajolet
authors: Paul
authors: P
authors: Greengard
mesh_terms: D000818:Animals; D047310:Apigenin / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D047310:Apigenin; D000242:Cyclic AMP; D047390:Casein Kinase II