Coupling of dopamine receptors to G proteins: studies with chimeric D2/D3 dopamine receptors.
D2 and D3 dopamine receptors belong to the superfamily of G protein-coupled receptors; they share a high degree of homology and are structurally similar. However, they differ from each other in their second messenger coupling properties. Previously, we have studied the differential coupling of these receptors to G proteins and found that while D2 receptor couples only to inhibitory G proteins, D3 receptor couples also to a stimulatory G protein, Gs. We aimed to investigate the molecular basis of these differences and to determine which domains in the receptor control its coupling to G proteins. For this purpose four chimeras were constructed, each composed of different segments of the original D2 and D3 receptors. We have demonstrated that chimeras with a third cytoplasmic loop of D2 receptor couple to Gi protein in a pattern characteristic of D2 receptor. On the other hand chimeras containing a third cytoplasmic loop of D3 receptor have coupling characteristics like those of D3 receptor, and they couple also to Gs protein. These findings demonstrate that the third cytoplasmic loop determines and accounts for the coupling of dopamine receptors D2 and D3 to G proteins.
Ilani
Tal
T
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Fishburn
C Simone
CS
Levavi-Sivan
Berta
B
Carmon
Shari
S
Raveh
Lily
L
Fuchs
Sara
S
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008958:Models, Molecular; D037342:Pertussis Toxin / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D050637:Receptors, Dopamine D3; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011993:Recombinant Fusion Proteins; D019257:Quinpirole; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine