Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 33, Pages 14096-14101Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0906857106
Keywords
dopamine 1 receptor; GPCR; striatum; casein kinase 2; adenosine A2A receptor
Categories
Funding
- National Institutes of Health [DA10044, MH074866]
- USA Medical Research and Materiel Command NETRP program [W81XWH-05-1-0146]
- Picower Foundation
- Japan Society for the Promotion of Science [18300128]
- Rockefeller University Women and Science
- Grants-in-Aid for Scientific Research [18300128] Funding Source: KAKEN
Ask authors/readers for more resources
We present evidence, using biochemical and cellular approaches, that the kinase, CK2, negatively controls signaling via G alpha(s) (or G alpha(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 G alpha(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 G alpha(s).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available