Phosducin inhibits receptor phosphorylation by the beta-adrenergic receptor kinase in a PKA-regulated manner.
Homologous or receptor-specific desensitization of beta-adrenergic receptors is thought to be triggered by receptor phosphorylation mediated by the beta-adrenergic receptor kinases (beta ARK). Upon receptor activation, cytosolic beta ARK translocates to the membrane, probably by binding to G-protein beta gamma-subunits. Using the purified proteins reconstituted into phospholipid vesicles we show here that this binding process can be inhibited by phosducin, a cytosolic protein that has recently been described as a regulator of G-protein-mediated signalling. Phosducin appears to complete very effectively with beta ARK for the G-protein beta gamma-subunits. These inhibitory effects of phosducin on receptor phosphorylation are antagonized following phosphorylation of phosducin by protein kinase A. It is proposed that phosducin may act as a regulator of homologous beta-adrenergic receptor desensitization.
Hekman
M
M
Laboratory of Molecular Biology, University of Munich, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
Bauer
P H
PH
Söhlemann
P
P
Lohse
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005136:Eye Proteins / Q000494:pharmacology*; D020555:GTP-Binding Protein Regulators; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000494:pharmacology*; D010766:Phosphorylation; D015398:Signal Transduction; D051552:beta-Adrenergic Receptor Kinases
D005136:Eye Proteins; D020555:GTP-Binding Protein Regulators; D010750:Phosphoproteins; C065631:phosducin; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D019204:GTP-Binding Proteins