TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity.

Proceedings of the National Academy of Sciences of the United States of America
Qian YangKun-Liang Guan

Abstract

Target of rapamycin (TOR) plays a central role in cell growth regulation by integrating signals from growth factors, nutrients, and cellular energy levels. TOR forms two distinct physical and functional complexes, termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2). TORC1, which is sensitive to rapamycin, regulates translation and cell growth, whereas TORC2, which is insensitive to rapamycin, regulates cell morphology and cell growth. The Ras homology enriched in brain (Rheb) small GTPase is known to be a key upstream activator of TORC1, although the mechanism of Rheb in TORC1 activation remains to be determined. However, the function of Rheb in the TORC2 regulation has not been elucidated. By measuring Akt and S6K phosphorylation as a functional assay for TORC1 and -2, here, we report that dRheb has an inhibitory effect on dTORC2 activity in Drosophila S2 cells. This negative effect of dRheb on dTORC2 is possibly due to a feedback mechanism involving dTORC1 and dS6K. We also observed that Rheb does not activate TORC2 in human embryonic kidney 293 cells, although it potently stimulates TORC1. Furthermore, tuberous sclerosis complex 1 (TSC1) and TSC2, which are negative regulators of Rheb, have negative and positive effects o...Continue Reading

References

Feb 21, 1998·Science·N PullenG Thomas
Jun 13, 1998·Human Molecular Genetics·M van SlegtenhorstP van der Sluijs
Nov 10, 2001·Trends in Biochemical Sciences·D P Brazil, B A Hemmings
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·K A Mowen, M David
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·C A WorbyJ E Dixon
Feb 28, 2002·Nature Cell Biology·Thomas RadimerskiGeorge Thomas
Apr 23, 2002·Current Biology : CB·Stefanie S Schalm, John Blenis
Aug 13, 2002·Nature Cell Biology·Ken InokiKun-Liang Guan
Aug 13, 2002·Nature Cell Biology·Xinsheng GaoDuojia Pan
Jan 31, 2003·Annals of Human Genetics·D J Kwiatkowski
Feb 4, 2003·Nature Reviews. Molecular Cell Biology·Estela Jacinto, Michael N Hall
May 27, 2003·Nature Cell Biology·Hugo StockerErnst Hafen
May 27, 2003·Nature Cell Biology·Leslie J SaucedoBruce A Edgar
May 29, 2003·Nature Cell Biology·Yong ZhangDuojia Pan
Jul 19, 2003·Genes & Development·Ken InokiKun-Liang Guan
Dec 12, 2003·Science's STKE : Signal Transduction Knowledge Environment·Thurl E Harris, John C Lawrence
Apr 23, 2004·Trends in Cell Biology·Duojia PanXinsheng Gao
Jul 14, 2004·The Journal of Cell Biology·Laura S HarringtonRichard F Lamb
Oct 7, 2004·Nature Cell Biology·Estela JacintoMichael N Hall
Feb 19, 2005·Science·D D SarbassovDavid M Sabatini
Apr 6, 2005·The Journal of Biological Chemistry·Siraj M Ali, David M Sabatini
Apr 28, 2005·Current Biology : CB·Xiaomeng LongJoseph Avruch
Aug 2, 2005·Molecular and Cellular Biology·Yoshiaki KamadaYoshinori Ohsumi
Oct 13, 2005·Journal of Cell Science·Barry J CollinsDario R Alessi

❮ Previous
Next ❯

Citations

Feb 7, 2013·Acta Neuropathologica·Peter B Crino
Jul 2, 2009·Journal of Chemical Biology·Lisa M Ballou, Richard Z Lin
Aug 8, 2007·Cell Research·Qian Yang, Kun-Liang Guan
Jan 12, 2010·Nature Neuroscience·Duyu NieMustafa Sahin
Mar 4, 2008·Nature Reviews. Microbiology·Nicholas J BuchkovichJames C Alwine
Dec 24, 2010·The Journal of Biological Chemistry·Jun SunShu-Bing Qian
Oct 10, 2008·The Journal of Biological Chemistry·Ying-Hua LiAndreas W Püschel
Mar 21, 2009·The Journal of Biological Chemistry·Tatsuhiro SatoFuyuhiko Tamanoi
Feb 9, 2013·Human Molecular Genetics·Rajalaxmi NatarajanYogesh P Wairkar
Aug 19, 2007·Epilepsia·David Neal Franz
Mar 30, 2012·Science Signaling·Piero Dalle PezzeKathrin Thedieck
Apr 16, 2008·Molecular and Cellular Biology·Jingxiang HuangBrendan D Manning
Apr 12, 2012·Molecular and Cellular Biology·Tao WangBruce A Edgar
Sep 14, 2006·Annual Review of Pharmacology and Toxicology·Chung-Han LeeKun-Liang Guan
Aug 20, 2009·American Journal of Physiology. Endocrinology and Metabolism·Hiroyuki MoriKun-Liang Guan
May 28, 2009·BMC Molecular Biology·Xuan ZhangCong-Zhao Zhou
Mar 19, 2013·Skeletal Muscle·C Florian BentzingerMarkus A Rüegg
Jul 28, 2011·Development·Ryan C RussellKun-Liang Guan
Jun 30, 2010·PLoS Genetics·Lutz KockelNorbert Perrimon
Nov 22, 2007·PloS One·Kathrin ThedieckMichael N Hall
Apr 4, 2007·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Vera P Krymskaya
Apr 7, 2011·Experimental & Molecular Medicine·Chang Hoon Cho
Oct 20, 2012·Cerebral Cortex·Victoria TsaiPeter B Crino
Jul 25, 2012·Molecular Neurobiology·Emilio RussoGiovambattista De Sarro
Dec 17, 2014·Molecular Biology International·Mehvish ShowkatKhurshid I Andrabi
Jan 31, 2013·The Journal of Biological Chemistry·Anna R MalikJacek Jaworski
Sep 21, 2011·The Journal of Cell Biology·Lunhua Liu, Carole A Parent
Jun 21, 2006·The Journal of Cell Biology·Krista M HennigThomas P Neufeld
Feb 19, 2011·FEBS Letters·Juliette M Han, Mustafa Sahin
Aug 4, 2015·International Journal of Cancer. Journal International Du Cancer·Marisol E ArmijoAriel F Castro

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.