TY - JOUR T1 - Mechanisms of biased beta-arrestin mediated signaling downstream from the cannabinoid 1 receptor JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.115.103176 SP - mol.115.103176 AU - Francheska Delgado-Peraza AU - Kwang Ahn AU - Carlos Nogueras-Ortiz AU - Imran Mungrue AU - Ken P. Mackie AU - Debra A. Kendall AU - Guillermo Yudowski Y1 - 2016/01/01 UR - http://molpharm.aspetjournals.org/content/early/2016/03/23/mol.115.103176.abstract N2 - Activation of G protein-coupled receptors (GPCR) result in multiple waves of signaling which are mediated by heterotrimeric G proteins and the scaffolding proteins β-arrestin 1/ 2. Ligands can elicit full or subsets of cellular responses, a concept defined sometimes as ligand bias or functional selectivity. However, our current understanding of beta-arrestin mediated signaling is still very limited. Here we provide a comprehensive view of β-arrestin mediated signaling from the cannabinoid receptor 1 (CB1R). Utilizing a signaling biased receptor, we define the cascades, specific receptor kinases and molecular mechanism underlying β-arrestin mediated signaling: We identify the interaction kinetics of CB1R and β-arrestin 1 during their endocytic trafficking as directly proportional to its efficacy. Finally, we demonstrate that signaling results in the control of genes clustered around prosurvival and proapoptotic functions among others. Together, these studies constitute a comprehensive description of β-arrestin mediated signaling from CB1Rs and suggest modulation of receptor endocytic trafficking as a therapeutic approach to control β-arrestin mediated signaling. ER -