Rheb Binds and Regulates the mTOR Kinase

Long, Samuel; Lin, Yenshou; Ortiz-Vega, Sara; Yonezawa, Kazuyoshi; Avruch, Joseph

doi:10.1016/j.cub.2005.02.053

Cited by 885 publications

(816 citation statements)

References 45 publications

Supporting

Mentioning

751

Contrasting

Unclassified

Order By: Relevance

“…As a result, phosphorylated TSC2 is no longer able to interact with its functional partner TSC1, leading to a loss of protein stability and activity (Potter et al, 2002). The concomitant increase in RHEB-GTP activates mTOR when it resides in a multifunctional complex termed mTORC1 (Long et al, 2005). The rapamycin-sensitive mTORC1 complex activates p70S6K (to increase translation) and inhibits 4E-BP1 (to block translation initiation inhibition) .…”

Section: Pten/pi3k Signaling Perturbations In Cancermentioning

confidence: 99%

The role of PTEN signaling perturbations in cancer and in targeted therapy

2008

View full text Add to dashboard Cite

The PTEN tumor suppressor was discovered by its homozygous deletion and other mutations in cancer. Since then, PTEN has been shown to be a non-redundant, evolutionarily conserved phosphatase whose function affects diverse cellular progresses such as cell cycle progression, cell proliferation, chemotaxis, apoptosis, aging, muscle contractility, DNA damage response, angiogenesis and cell polarity. In accordance with its ability to influence multiple crucial cellular processes, PTEN has a major role in the pathogenesis of numerous diseases such as diabetes, autism and almost every cancer examined. This review will discuss the diverse ways in which PTEN signaling is modified in cancer, and how these changes correlate with and might possibly affect the action of targeted chemotherapy.

show abstract

Section: Pten/pi3k Signaling Perturbations In Cancermentioning

confidence: 99%

The role of PTEN signaling perturbations in cancer and in targeted therapy

2008

View full text Add to dashboard Cite

show abstract

“…PKB/Akt may also indirectly antagonize TSC2 function by virtue of its ability to maintain cellular energy reserves that prevent AMPK activation (see below; Hahn-Windgassen et al, 2005). TSC2 stimulates the GTPase activity of the small GTP-binding protein Rheb, which directly interacts with and positively regulates mTORC1 (Long, Lin, Ortiz-Vega, Yonezawa, & Avruch, 2005). Ligation of hormone and growth factor receptors also lead to increased activity of RasGEFs and decreased activity of RasGAPs (e.g.…”

Section: Regulation Of Mtorc1 By Hormones and Growth Factorsmentioning

confidence: 99%

The TOR signalling network from yeast to man

Virgilio

Loewith

2006

The International Journal of Biochemistry & Cell Biology

207

162

View full text Add to dashboard Cite

The target of rapamycin, TOR, is an essential ser/thr protein kinase that functions in two distinct multiprotein complexes, TOR complex 1 and 2. The structure and functions of these complexes have been conserved from yeast to man. TOR complex 1 is inhibited by rapamycin and is thought to couple growth cues to cellular metabolism; TOR complex 2 is not inhibited by rapamycin and appears to regulate spatial aspects of growth such as cell polarity. Work done in a variety of model systems, continues to contribute to our current understanding of this TOR signalling network. Recent studies in flies and mammalian tissue culture cells have elucidated many signalling components upstream of TOR complex 1. These studies also suggest that aberrant mammalian TOR complex 1 signalling contributes to a number of pathologies ranging from metabolic diseases to hyperproliferative disorders and cancers. Consequently the efficacies of rapamycin and related compounds in treating such diseases are being evaluated in clinical trials.

show abstract

“…dRheb overexpression recapitulates dTSC1/2 mutant phenotypes, and reduction in dRheb function rescues larval lethality caused by loss of dTSC1/2 in the fly . Furthermore, Rheb has recently been shown to bind to mTOR independent of its guanyl nucleotide charging, but GTP loading determines TOR kinase activity (Long et al, 2005). mTOR substrates include the inhibitory eIF4E-binding proteins (4E-BP1-3, collectively referred to as 4E-BPs) and the ribosomal kinases S6K1/S6K2 (henceforth referred to as S6K).…”

Section: Introductionmentioning

confidence: 99%