Vistein, Rachel Puthenveedu, Manojkumar Reprogramming of G protein-coupled receptor recycling and signaling by a kinase switch. <p>The postendocytic recycling of signaling receptors is subject to multiple requirements. Why this is so, considering that many other proteins can recycle without apparent requirements, is a fundamental question. Here we show that cells can leverage these requirements to switch the recycling of the beta-2 adrenergic receptor (B2AR), a prototypic signaling receptor, between sequence-dependent and bulk recycling pathways, based on extracellular signals. This switch is determined by protein kinase A-mediated phosphorylation of B2AR on the cytoplasmic tail. The phosphorylation state of B2AR dictates its partitioning into spatially and functionally distinct endosomal microdomains mediating bulk and sequence-dependent recycling, and also regulates the rate of B2AR recycling and resensitization. Our results demonstrate that G protein-coupled receptor recycling is not always restricted to the sequence-dependent pathway, but may be reprogrammed as needed by physiological signals. Such flexible reprogramming might provide a versatile method for rapidly modulating cellular responses to extracellular signaling.</p> Cyclic AMP-Dependent Protein Kinases;Endosomes;HEK293 Cells;Humans;Microscopy;Confocal;Models;Biological;Phosphorylation;Proteolysis;Receptors;Adrenergic;beta-2;Signal Transduction 2013-09-17
    https://kilthub.cmu.edu/articles/journal_contribution/Reprogramming_of_G_protein-coupled_receptor_recycling_and_signaling_by_a_kinase_switch_/6104162
10.1184/R1/6104162.v1