β 2 -Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein
| Autor: | Audrey Claing, Robert J. Lefkowitz, Martha Vaughan, Walter A. Patton, Joel Moss, Jennifer L. Freeman, Richard T. Premont, Julie A. Pitcher, Nicolas Vitale |
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| Rok vydání: | 1998 |
| Předmět: |
Male
G-Protein-Coupled Receptor Kinase 2 GTPase-activating protein ADP ribosylation factor Molecular Sequence Data Gene Expression Cell Cycle Proteins Spodoptera Biology Transfection Cell Line GTP-Binding Proteins Enzyme-linked receptor Animals Humans 5-HT5A receptor Amino Acid Sequence Coagulation factor II receptor Protease-activated receptor 2 Adaptor Proteins Signal Transducing G protein-coupled receptor G protein-coupled receptor kinase Binding Sites Multidisciplinary ADP-Ribosylation Factors Cell Membrane GTPase-Activating Proteins Proteins Biological Sciences Phosphoproteins Rod Cell Outer Segment Cyclic AMP-Dependent Protein Kinases Recombinant Proteins Cell biology Kinetics Organ Specificity beta-Adrenergic Receptor Kinases Cattle Receptors Adrenergic beta-2 |
| Zdroj: | Proceedings of the National Academy of Sciences. 95:14082-14087 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | G protein-coupled receptor activation leads to the membrane recruitment and activation of G protein-coupled receptor kinases, which phosphorylate receptors and lead to their inactivation. We have identified a novel G protein-coupled receptor kinase-interacting protein, GIT1, that is a GTPase-activating protein (GAP) for the ADP ribosylation factor (ARF) family of small GTP-binding proteins. Overexpression of GIT1 leads to reduced β 2 -adrenergic receptor signaling and increased receptor phosphorylation, which result from reduced receptor internalization and resensitization. These cellular effects of GIT1 require its intact ARF GAP activity and do not reflect regulation of GRK kinase activity. These results suggest an essential role for ARF proteins in regulating β 2 -adrenergic receptor endocytosis. Moreover, they provide a mechanism for integration of receptor activation and endocytosis through regulation of ARF protein activation by GRK-mediated recruitment of the GIT1 ARF GAP to the plasma membrane. |
| Databáze: | OpenAIRE |
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