title: Beta-arrestin-mediated signaling regulates protein synthesis.
abstract: Seven transmembrane receptors (7TMRs) exert strong regulatory influences on virtually all physiological processes. Although it is historically assumed that heterotrimeric G proteins mediate these actions, there is a newer appreciation that beta-arrestins, originally thought only to desensitize G protein signaling, also serve as independent receptor signal transducers. Recently, we found that activation of ERK1/2 by the angiotensin receptor occurs via both of these distinct pathways. In this work, we explore the physiological consequences of beta-arrestin ERK1/2 signaling and delineate a pathway that regulates mRNA translation and protein synthesis via Mnk1, a protein that both physically interacts with and is activated by beta-arrestins. We show that beta-arrestin-dependent activation of ERK1/2, Mnk1, and eIF4E are responsible for increasing translation rates in both human embryonic kidney 293 and rat vascular smooth muscle cells. This novel demonstration that beta-arrestins regulate protein synthesis reveals that the spectrum of beta-arrestin-mediated signaling events is broader than previously imagined.
authors.affiliation: Department of Medicine and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: DeWire
authors.forename: Jihee
authors.initials: J
authors.lastname: Kim
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Whalen
authors.forename: Seungkirl
authors.initials: S
authors.lastname: Ahn
authors.forename: Minyong
authors.initials: M
authors.lastname: Chen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lefkowitz
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D047908:Intracellular Signaling Peptides and Proteins; D000071557:beta-Arrestins; C491395:MKNK1 protein, human; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3