Dopamine D2 receptor relies upon PPM/PP2C protein phosphatases to dephosphorylate huntingtin protein. / Marion, S; Urs, NM; Peterson, SM; Sotnikova, TD; Beaulieu, JM; Gainetdinov, RR; Caron, MG.
In: Journal of Biological Chemistry, 2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dopamine D2 receptor relies upon PPM/PP2C protein phosphatases to dephosphorylate huntingtin protein.
AU - Marion, S
AU - Urs, NM
AU - Peterson, SM
AU - Sotnikova, TD
AU - Beaulieu, JM
AU - Gainetdinov, RR
AU - Caron, MG.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Akt
KW - Arrestin
KW - Dopamine D2 Receptor
KW - Dopamine Receptors
KW - G Protein-coupled Receptors (GPCR)
KW - G Proteins
KW - Huntingtin
KW - PP2C
KW - Phosphatase
M3 - статья
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
ER -
ID: 5835623