Dopamine D2 receptor relies upon PPM/PP2C protein phosphatases to dephosphorylate huntingtin protein
| Autor: | Raul R. Gainetdinov, Jean-Martin Beaulieu, Sean M. Peterson, Sébastien Marion, Nikhil M. Urs, Tatyana D. Sotnikova, Marc G. Caron |
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| Rok vydání: | 2014 |
| Předmět: |
Huntingtin
Nerve Tissue Proteins Biology Biochemistry Dephosphorylation Mice Dopamine receptor D2 Huntingtin Protein Arrestin Phosphoprotein Phosphatases Animals Humans Phosphorylation Molecular Biology Protein kinase B Mice Knockout Receptors Dopamine D2 Nuclear Proteins Cell Biology Cell biology HEK293 Cells Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 289(17) |
| ISSN: | 1083-351X |
| Popis: | Striatal dopamine D2 receptor (D2R) relies upon G protein- and β-arrestin-dependent signaling pathways to convey its action on motor control and behavior. Considering that D2R activation inhibits Akt in the striatum and that huntingtin physiological functions are affected by Akt phosphorylation, we sought to investigate whether D2R-mediated signaling could regulate huntingtin phosphorylation. We demonstrate that D2R activation decreases huntingtin phosphorylation on its Akt site. This dephosphorylation event depends upon the Gαi-dependent engagement of specific members of the protein phosphatase metallo-dependent (PPM/PP2C) family and is independent of β-arrestin 2. These observations identify the PPM/PP2C family as a mediator of G protein-coupled receptor signaling and thereby suggest a novel mechanism of dopaminergic signaling. |
| Databáze: | OpenAIRE |
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