Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.

doi:10.1016/J.CUB.2004.06.054

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Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.

Journal Article•DOI•

Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.

Dos D. Sarbassov¹, Siraj M. Ali¹, Do Hyung Kim¹, David A. Guertin¹, Robert R. Latek¹, Hediye Erdjument-Bromage², Paul Tempst², David M. Sabatini¹ - Show less +4 more•Institutions (2)

Massachusetts Institute of Technology¹, Memorial Sloan Kettering Cancer Center²

27 Jul 2004-Current Biology (Cell Press)-Vol. 14, Iss: 14, pp 1296-1302

TL;DR: It is found that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals.

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About: This article is published in Current Biology.The article was published on 2004-07-27 and is currently open access. It has received 2609 citations till now. The article focuses on the topics: mTORC2 & RPTOR.

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mTOR Signaling in Growth Control and Disease

[...]

Mathieu Laplante¹, David M. Sabatini¹•Institutions (1)

Massachusetts Institute of Technology¹

01 Apr 2012

TL;DR: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis as mentioned in this paper, and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration.

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Abstract: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation.

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6,268 citations

Journal Article•DOI•

mTOR signaling in growth control and disease.

[...]

Mathieu Laplante¹, David M. Sabatini¹•Institutions (1)

Massachusetts Institute of Technology¹

13 Apr 2012-Cell

TL;DR: Recent advances in understanding of the mTOR pathway are reviewed and pharmacological approaches to treat human pathologies linked to mTOR deregulation are discussed.

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5,792 citations

Cites background from "Rictor, a novel binding partner of ..."

...…Vander Haar et al., 2007; Wang et al., 2007) are specific to mTORC1, whereas rapamycin-insensitive companion of mTOR (rictor) (Jacinto et al., 2004; Sarbassov et al., 2004), mammalian stress-activated map kinase-interacting protein 1 (mSin1) (Frias et al., 2006; Jacinto et al., 2006), and protein…...
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...Because acute treatment with rapamycin does not perturb mTORC2 signaling and FKBP12-rapamycin cannot bind to intact mTORC2, this complex was originally thought to be rapamycin insensitive (Jacinto et al., 2004; Sarbassov et al., 2004)....
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...Leading Edge Review mTOR Signaling in Growth...
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...…GTPases, the activation of PKC-a by mTORC2 regulates cell shape in celltype-specific fashion by affecting the actin cytoskeleton (Jacinto et al., 2004; Sarbassov et al., 2004) (Figure 2B). mTOR Signaling in Cancer Several observations support the importance of mTOR pathway in cancer pathogenesis....
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Journal Article•DOI•

TOR signaling in growth and metabolism.

[...]

Stephan Wullschleger¹, Robbie Loewith², Michael N. Hall¹•Institutions (2)

University of Basel¹, University of Geneva²

10 Feb 2006-Cell

TL;DR: The physiological consequences of mammalianTORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders.

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5,553 citations

Cites background or methods or result from "Rictor, a novel binding partner of ..."

...mTORC2 also signals to the actin cytoskeleton (Jacinto et al., 2004; Sarbassov et al., 2004)....
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...Also consistent with studies in model organisms is the observation that mTORC2 is neither bound by FKBP12-rapamycin nor does FKBP12-rapamycin affect mTORC2 in vitro kinase activity (Jacinto et al., 2004; Sarbassov et al., 2004)....
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...Knockdown of the mammalian, worm, and fly versions of KOG1/raptor phenocopies rapamycin treatment and/or depletion of TOR in these organisms, indicating that raptor functions positively in mTOR signaling (Hara et al., 2002; Kim et al., 2002; Sarbassov et al., 2004)....
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...As discussed below, mTORC1 also appears to regulate temporal aspects of cell growth. mTORC1 is bound by FKBP12-rapamycin, and mTORC1 kinase activity is abrogated by FKBP12-rapamycin both in vivo and in vitro (Hara et al., 2002; Jacinto et al., 2004; Kim et al., 2002; Sarbassov et al., 2004)....
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...These are the names used in the first of the two binding studies that were published for each protein (Loewith et al., 2002; Sarbassov et al., 2004)....
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Patent•DOI•

Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex

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David M. Sabatini¹, Dos D. Sarbassov¹•Institutions (1)

Massachusetts Institute of Technology¹

27 Jan 2006-Science

TL;DR: In this paper, the rictor-mTOR complex was used to identify compounds which modulate Akt activity mediated by the Rictor mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activation.

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Abstract: In certain aspects, the invention relates to methods for identifying compounds which modulate Akt activity mediated by the rictor-mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activity.

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5,430 citations

Journal Article•DOI•

mTOR Signaling in Growth, Metabolism, and Disease.

[...]

Robert A. Saxton, David M. Sabatini

09 Mar 2017-Cell

TL;DR: Recent advances in understanding of mTOR function, regulation, and importance in mammalian physiology are reviewed and how the mTOR signaling network contributes to human disease is highlighted.

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4,719 citations

Cites background from "Rictor, a novel binding partner of ..."

...The first mTORC2 substrate to be identified was PKCa, a regulator of the actin cytoskeleton (Jacinto et al., 2004; Sarbassov et al., 2004)....
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...…contains Rictor (rapamycin insensitive companion of mTOR), an unrelated protein that likely serves an analogous function (Jacinto et al., 2004; Sarbassov et al., 2004). mTORC2 also containsDEPTOR (Peterson et al., 2009), aswell as the regulatory subunitsmSin1 (Frias et al., 2006; Jacinto et…...
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...mTORC2 contains Rictor (rapamycin insensitive companion of mTOR), an unrelated protein that likely serves an analogous function (Jacinto et al., 2004; Sarbassov et al., 2004)....
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References

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Open Access

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Journal Article•DOI•

The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.

[...]

Julie D. Thompson¹, Toby J. Gibson, Frederica Plewniak¹, Francois Jeanmougin¹, Desmond G. Higgins² - Show less +1 more•Institutions (2)

French Institute of Health and Medical Research¹, University College Cork²

01 Dec 1997-Nucleic Acids Research

TL;DR: ClUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W, providing an integrated system for performing multiple sequence and profile alignments and analysing the results.

...read moreread less

Abstract: CLUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W. The new system is easy to use, providing an integrated system for performing multiple sequence and profile alignments and analysing the results. CLUSTAL X displays the sequence alignment in a window on the screen. A versatile sequence colouring scheme allows the user to highlight conserved features in the alignment. Pull-down menus provide all the options required for traditional multiple sequence and profile alignment. New features include: the ability to cut-and-paste sequences to change the order of the alignment, selection of a subset of the sequences to be realigned, and selection of a sub-range of the alignment to be realigned and inserted back into the original alignment. Alignment quality analysis can be performed and low-scoring segments or exceptional residues can be highlighted. Quality analysis and realignment of selected residue ranges provide the user with a powerful tool to improve and refine difficult alignments and to trap errors in input sequences. CLUSTAL X has been compiled on SUN Solaris, IRIX5.3 on Silicon Graphics, Digital UNIX on DECstations, Microsoft Windows (32 bit) for PCs, Linux ELF for x86 PCs, and Macintosh PowerMac.

...read moreread less

38,522 citations

Proceedings Article•

Fitting a mixture model by expectation maximization to discover motifs in biopolymers.

[...]

Timothy L. Bailey¹, Charles Elkan•Institutions (1)

University of California, San Diego¹

01 Jan 1994

TL;DR: The algorithm described in this paper discovers one or more motifs in a collection of DNA or protein sequences by using the technique of expectation maximization to fit a two-component finite mixture model to the set of sequences.

...read moreread less

Abstract: The algorithm described in this paper discovers one or more motifs in a collection of DNA or protein sequences by using the technique of expectation maximization to fit a two-component finite mixture model to the set of sequences Multiple motifs are found by fitting a mixture model to the data, probabilistically erasing the occurrences of the motif thus found, and repeating the process to find successive motifs The algorithm requires only a set of unaligned sequences and a number specifying the width of the motifs as input It returns a model of each motif and a threshold which together can be used as a Bayes-optimal classifier for searching for occurrences of the motif in other databases The algorithm estimates how many times each motif occurs in each sequence in the dataset and outputs an alignment of the occurrences of the motif The algorithm is capable of discovering several different motifs with differing numbers of occurrences in a single dataset

...read moreread less

4,978 citations

Journal Article•DOI•

mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery

[...]

Do Hyung Kim¹, Dos D. Sarbassov¹, Siraj M. Ali¹, Jessie E. King¹, Robert R. Latek¹, Hediye Erdjument-Bromage², Paul Tempst², David M. Sabatini¹ - Show less +4 more•Institutions (2)

Massachusetts Institute of Technology¹, Memorial Sloan Kettering Cancer Center²

26 Jul 2002-Cell

TL;DR: It is reported that mTOR forms a stoichiometric complex with raptor, an evolutionarily conserved protein with at least two roles in the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels.

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2,902 citations

Journal Article•DOI•

Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control

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Robbie Loewith¹, Estela Jacinto¹, Stephan Wullschleger¹, Anja Lorberg¹, José L. Crespo¹, Debora Bonenfant¹, Wolfgang Oppliger¹, Paul Jenoe¹, Michael N. Hall¹ - Show less +5 more•Institutions (1)

University of Basel¹

01 Sep 2002-Molecular Cell

TL;DR: Two functionally distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling.

...read moreread less

1,769 citations

Journal Article•DOI•

Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.

[...]

Kenta Hara¹, Yoshiko Maruki¹, Xiaomeng Long², Ken-ichi Yoshino¹, Noriko Oshiro¹, Sujuti Hidayat¹, Chiharu Tokunaga¹, Joseph Avruch², Kazuyoshi Yonezawa¹ - Show less +5 more•Institutions (2)

Kobe University¹, Harvard University²

26 Jul 2002-Cell

TL;DR: Raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo and yields an array of phenotypes that closely resemble those produced by inactivation of Ce-TOR.

...read moreread less

1,752 citations