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CK2 Negatively Regulates ${\rm{G\alpha }}_{\rm{s}} $ Signaling

Heike Rebholz, Akinori Nishi, Sabine Liebscher, Angus C. Nairn, Marc Flajolet and Paul Greengard
Proceedings of the National Academy of Sciences of the United States of America
Vol. 106, No. 33 (Aug. 18, 2009), pp. 14096-14101
Stable URL: http://www.jstor.org/stable/40484373
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
CK2 Negatively Regulates
          ${\rm{G\alpha }}_{\rm{s}} $
          Signaling
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Abstract

We present evidence, using biochemical and cellular approaches, that the kinase, CK2, negatively controls signaling via ${\rm{G\alpha }}_{\rm{s}} $ (or ${\rm{G\alpha }}_{{\rm{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 β subunit of CK2 was found to interact specifically with the ${\rm{G\alpha }}_{\rm{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 ${\rm{G\alpha }}_{\rm{s}} $.

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