Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors.
The rate and extent of the agonist-dependent phosphorylation of beta 2-adrenergic receptors and rhodopsin by beta-adrenergic receptor kinase (beta ARK) are markedly enhanced on addition of G protein beta gamma subunits. With a model peptide substrate it was demonstrated that direct activation of the kinase could not account for this effect. G protein beta gamma subunits were shown to interact directly with the COOH-terminal region of beta ARK, and formation of this beta ARK-beta gamma complex resulted in receptor-facilitated membrane localization of the enzyme. The beta gamma subunits of transducin were less effective at both enhancing the rate of receptor phosphorylation and binding to the COOH-terminus of beta ARK, suggesting that the enzyme preferentially binds specific beta gamma complexes. The beta gamma-mediated membrane localization of beta ARK serves to intimately link receptor activation to beta ARK-mediated desensitization.
Pitcher
J A
JA
Howard Hughes Medical Research Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Inglese
J
J
Higgins
J B
JB
Arriza
J L
JL
Casey
P J
PJ
Kim
C
C
Benovic
J L
JL
Kwatra
M M
MM
Caron
M G
MG
Lefkowitz
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D017868:Cyclic AMP-Dependent Protein Kinases; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D019204:GTP-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012243:Rhodopsin / Q000378:metabolism; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D051552:beta-Adrenergic Receptor Kinases
D011943:Receptors, Adrenergic, beta; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; D012243:Rhodopsin; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D019204:GTP-Binding Proteins