Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb.

By Andrew R. Tee, B. Manning, Philippe P Roux, Lewis C. Cantley, J. Blenis. Current Biology, 2003

1,260 citations recorded by the source corpus.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/3913bd1cbab8b412075d594a79910848c38348d6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. David M. Sabatini
2. M. Laplante
3. K. Guan
4. B. Manning
5. R. A. Saxton
6. M. V. Vander Heiden
7. Ralph J. Deberardinis
8. Young Chul Kim

In Physiology

1. David M. Sabatini
2. K. Guan
3. B. Manning
4. M. Laplante
5. Jingxiang Huang
6. M. Karin
7. A. Budanov
8. Young Chul Kim

Citations in the corpus

• mTOR signaling at a glance (2009, background): “As a Rheb-specific GAP, TSC1/2 negatively regulates mTORC1 signaling by converting Rheb into its inactive GDP-bound state (Inoki et al., 2003; Tee et al., 2003).”
• Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. (2012, neutral): “When bound to GTP, Rheb interacts with and activates mTORC1 (Tee et al., 2003) and is necessary for the activation of mTORC1 by all signals, including amino acid availability.”
• The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis (2012, positive): “TSC2 is a GTPase activating protein (GAP) for the small GTPase Rheb, a protein that promotes the activation of mTORC1 (44, 45).”
• PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. (2007, background): “The mechanisms underlying mTORC1 regulation are not well understood, but a key upstream player is clearly the GTP binding protein rheb, which is negatively regulated by the dimeric TSC1-TSC2 GTPase-activating protein (GAP) (Castro et al., 2003; Garami et al., 2003; Inoki et al., 2003a; Saucedo et al”
• p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. (2008, positive): “Rheb GTP loading is controlled by the TSC1:TSC2 complex (Garami et al., 2003; Inoki et al., 2003b; Tee et al., 2003).”
• mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. (2013, background): “Ras-homolog enriched in brain (Rheb) is a small GTPase that activates mTORC1 (Inoki et al., 2003; Tee et al., 2003).”
• mTOR Signaling in Growth, Metabolism, and Disease. (2017, background): “, 2012), and functions as a GTPase activating protein (GAP) for the small GTPase Rheb (Inoki et al., 2003; Tee et al., 2003), which directly binds and activates mTORC1 (Long et al.”
• mTOR: a pharmacologic target for autophagy regulation. (2015, positive): “Activated AKT directly phosphorylates and thereby inhibits TSC1/2, a GTPase-activating protein (GAP) for the Ras homolog enriched in brain (Rheb) GTPase (19–23).”