We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Constitutive phosphorylation by protein kinase C regulates D.
- Authors
Rankin, Michele L.; Sibley, David R.
- Abstract
The D1 dopamine receptor (D1DAR) is robustly phosphorylated by multiple protein kinases, yet the phosphorylation sites and functional consequences of these modifications are not fully understood. Here, we report that the D1DAR is phosphorylated by protein kinase C (PKC) in the absence of agonist stimulation. Phosphorylation of the D1DAR by PKC is constitutive in nature, can be induced by phorbol ester treatment or through activation of Gq-mediated signal transduction pathways, and is abolished by PKC inhibitors. We demonstrate that most, but not all, isoforms of PKC are capable of phosphorylating the receptor. To directly assess the functional role of PKC phosphorylation of the D1DAR, a site-directed mutagenesis approach was used to identify the PKC sites within the receptor. Five serine residues were found to mediate the PKC phosphorylation. Replacement of these residues had no effect on D1DAR expression or agonist-induced desensitization; however, G protein coupling and cAMP accumulation were significantly enhanced in PKC-null D1DAR. Thus, constitutive or heterologous PKC phosphorylation of the D1DAR dampens dopamine activation of the receptor, most likely occurring in a context-specific manner, mediated by the repertoire of PKC isozymes within the cell.
- Subjects
PHOSPHORYLATION; PROTEIN kinases; PHOSPHOTRANSFERASES; CYCLIN-dependent kinases; GLYCOGEN synthase kinase-3; CHEMICAL reactions; PHOSPHORYLASES
- Publication
Journal of Neurochemistry, 2010, Vol 115, Issue 6, p1655
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2010.07074.x