β 2 -Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein

• DOI: 10.1073/pnas.95.24.14082
• Publication Date: 2002-07-26T14:42:40Z
• Authors: Richard T. Premont; Audrey Claing; Nicolas Vitale; Jennifer L. R. Fr...; Julie A. Pitcher; Walter A. Patton; Joel Moss; Martha Vaughan; Robert J. Lefkowitz
• Keywords: ADP ribosylation factor

G protein-coupled receptor activation leads to the membrane recruitment and of kinases, which phosphorylate receptors lead their inactivation. We have identified a novel kinase-interacting protein, GIT1, that is GTPase-activating protein (GAP) for ADP ribosylation factor (ARF) family small GTP-binding proteins. Overexpression GIT1 reduced β 2 -adrenergic signaling increased phosphorylation, result from internalization resensitization. These cellular effects require its intact ARF GAP activity do not reflect regulation GRK kinase activity. results suggest an essential role proteins in regulating endocytosis. Moreover, they provide mechanism integration endocytosis through by GRK-mediated plasma membrane.