title: Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2α Signaling Cascade.
abstract: Rheb, a ubiquitous small GTPase, is well known to bind and activate mTOR, which augments protein synthesis. Inhibition of protein synthesis is also physiologically regulated. Thus, with cell stress, the unfolded protein response system leads to phosphorylation of the initiation factor eIF2α and arrest of protein synthesis. We now demonstrate a major role for Rheb in inhibiting protein synthesis by enhancing the phosphorylation of eIF2α by protein kinase-like ER kinase (PERK). Interplay between the stimulatory and inhibitory roles of Rheb may enable cells to modulate protein synthesis in response to varying environmental stresses.
authors: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Richa
authors: R
authors: Tyagi
authors: Department of Neuroscience, The Scripps Research Institute, Florida, Jupiter, FL 33458, USA.
authors: Neelam
authors: N
authors: Shahani
authors: Harriet L. Wilkes Honors College, Florida Atlantic University, 5353 Parkside Drive, Jupiter, FL 33458, USA.
authors: Lindsay
authors: L
authors: Gorgen
authors: Department of Cancer Biology, The Scripps Research Institute, Florida, Jupiter, FL 33458, USA.
authors: Max
authors: M
authors: Ferretti
authors: Department of Neuroscience, The Scripps Research Institute, Florida, Jupiter, FL 33458, USA.
authors: William
authors: W
authors: Pryor
authors: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Po Yu
authors: PY
authors: Chen
authors: Department of Neuroscience, The Scripps Research Institute, Florida, Jupiter, FL 33458, USA.
authors: Supriya
authors: S
authors: Swarnkar
authors: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Paul F
authors: PF
authors: Worley
authors: Department of Cancer Biology, The Scripps Research Institute, Florida, Jupiter, FL 33458, USA.
authors: Katrin
authors: K
authors: Karbstein
authors: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: ssnyder@jhmi.edu.
authors: Solomon H
authors: SH
authors: Snyder
authors: Department of Neuroscience, The Scripps Research Institute, Florida, Jupiter, FL 33458, USA. Electronic address: ssubrama@scripps.edu.
authors: Srinivasa
authors: S
authors: Subramaniam