IDENTIFICATION OF A CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE-DEPENDENT PROTEIN-KINASE PHOSPHORYLATION SITE IN THE CARBOXY-TERMINAL TAIL OF HUMAN D-1 DOPAMINE-RECEPTOR

Each of the dopamine receptor subtypes contains several consensus site s for phosphorylation in their intracellular domains. We have used fus ion proteins of the carboxy terminal tail of D-1 and D-5 dopamine rece ptors to study the phosphorylation of these proteins by cyclic adenosi ne 3',5' monophosphate (cAMP)-dependent protein kinase (PKA) and prote in kinase C (PKC). The fusion protein of D-1 dopamine receptor was eff iciently phosphorylated by PKA, but not by PKC. Site-directed mutagene sis of serine 380 to an alanine residue precluded the phosphorylation by the kinase. No phosphorylation of the D-5 dopamine receptor fusion protein was observed with either PKA or PKC, which indicates that thes e receptor subtypes might differ in their mechanisms of regulation.