Beta-arrestin-mediated signaling regulates protein synthesis.
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.
DeWire, SM; Kim, J; Whalen, EJ; Ahn, S; Chen, M; Lefkowitz, RJ
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