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- Heike Rebholz
- Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065;
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- Akinori Nishi
- Department of Pharmacology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan; and
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- Sabine Liebscher
- Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065;
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- Angus C. Nairn
- Department of Psychiatry, Yale University School of Medicine, Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06508
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- Marc Flajolet
- Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065;
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- Paul Greengard
- Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065;
説明
<jats:p> We present evidence, using biochemical and cellular approaches, that the kinase, CK2, negatively controls signaling via Gα <jats:sub>s</jats:sub> (or Gα <jats:sub>olf</jats:sub> ) 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 β subunit of CK2 was found to interact specifically with the Gα <jats:sub>s</jats:sub> 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 Gα <jats:sub>s</jats:sub> . </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 106 (33), 14096-14101, 2009-08-18
Proceedings of the National Academy of Sciences