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Microbiology and Molecular Biology Reviews, March 2005, p. 79-100, Vol. 69, No. 1
1092-2172/05/$08.00+0     doi:10.1128/MMBR.69.1.79-100.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Signaling by Target of Rapamycin Proteins in Cell Growth Control

Ken Inoki,1,2,{dagger} Hongjiao Ouyang,1,3,{dagger} Yong Li,1,2 and Kun-Liang Guan1,2,4*

Life Sciences Institute,1 Department of Biological Chemistry,2 Department of Cariology, Restorative Sciences and Endodontics,3 Institute of Gerontology, University of Michigan, Ann Arbor, Michigan4

Target of rapamycin (TOR) proteins are members of the phosphatidylinositol kinase-related kinase (PIKK) family and are highly conserved from yeast to mammals. TOR proteins integrate signals from growth factors, nutrients, stress, and cellular energy levels to control cell growth. The ribosomal S6 kinase 1 (S6K) and eukaryotic initiation factor 4E binding protein 1(4EBP1) are two cellular targets of TOR kinase activity and are known to mediate TOR function in translational control in mammalian cells. However, the precise molecular mechanism of TOR regulation is not completely understood. One of the recent breakthrough studies in TOR signaling resulted in the identification of the tuberous sclerosis complex gene products, TSC1 and TSC2, as negative regulators for TOR signaling. Furthermore, the discovery that the small GTPase Rheb is a direct downstream target of TSC1-TSC2 and a positive regulator of the TOR function has significantly advanced our understanding of the molecular mechanism of TOR activation. Here we review the current understanding of the regulation of TOR signaling and discuss its function as a signaling nexus to control cell growth during normal development and tumorigenesis.

* Corresponding author. Mailing address: University of Michigan Medical School, 5450 Medical Science I Bldg., Ann Arbor, MI 48109-0606. Phone: (734) 763-3030. Fax: (734) 647-9702. E-mail: kunliang{at}umich.edu.

{dagger} K.I. and H.O. made equal contributions to this review.

Microbiology and Molecular Biology Reviews, March 2005, p. 79-100, Vol. 69, No. 1
1092-2172/05/$08.00+0     doi:10.1128/MMBR.69.1.79-100.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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