title: Reprogramming of G protein-coupled receptor recycling and signaling by a kinase switch.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA 15213.
authors.forename: Rachel
authors.initials: R
authors.lastname: Vistein
authors.forename: Manojkumar A
authors.initials: MA
authors.lastname: Puthenveedu
mesh_terms: D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D018613:Microscopy, Confocal; D008954:Models, Biological; D010766:Phosphorylation; D059748:Proteolysis; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018343:Receptors, Adrenergic, beta-2; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: catecholamine receptor; endosomal tubule; endosome; sorting