Degradation of the G protein-coupled receptor kinase 2 by the proteasome pathway.
GRK2 is a ubiquitous member of the G protein-coupled receptor kinase (GRK) family and has been shown to play a key role in determining the desensitization and resensitization patterns of a variety of G protein-coupled receptors. In this report, we show that GRK2 is actively degraded by the proteasome proteolytic pathway, unveiling a new mechanism for the rapid regulation of its expression levels. Interestingly, activation of beta2-adrenergic receptors (beta2AR) markedly increases GRK2 ubiquitination and degradation through the proteasome pathway. In addition, blocking GRK2 degradation notably alters beta2AR signaling and internalization, consistent with a relevant physiological role for GRK2 proteasomal degradation. Activity-dependent modulation of GRK2 cellular levels emerges as an important mechanism for modulating the cellular response to agonists acting through G protein-coupled receptors.
Penela
P
P
Departamento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Universidad Autónoma, E-28049 Madrid, Spain.
Ruiz-Gómez
A
A
Castaño
J G
JG
Mayor
F
F
D002474:Cell-Free System; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004705:Endocytosis; D004795:Enzyme Stability; D019204:GTP-Binding Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D009097:Multienzyme Complexes / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014452:Ubiquitins / Q000378:metabolism; D051552:beta-Adrenergic Receptor Kinases
D009097:Multienzyme Complexes; D010446:Peptide Fragments; D018343:Receptors, Adrenergic, beta-2; D011994:Recombinant Proteins; D014452:Ubiquitins; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D019204:GTP-Binding Proteins