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PI3K/AKT/mTOR pathway

About: PI3K/AKT/mTOR pathway is a(n) research topic. Over the lifetime, 51207 publication(s) have been published within this topic receiving 2130942 citation(s). The topic is also known as: PI3K/AKT/TOR pathway.

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Papers
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Open accessJournal ArticleDOI: 10.1016/S0092-8674(00)80595-4
Anne Brunet1, Azad Bonni1, Michael J. Zigmond1, Michael Z. Lin1  +6 moreInstitutions (2)
19 Mar 1999-Cell
Abstract: Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/ threonine kinase Akt, which then phosphorylates and inactivates components of the apoptotic machinery, including BAD and Caspase 9. In this study, we demonstrate that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors. In the presence of survival factors, Akt phosphorylates FKHRL1, leading to FKHRL1's association with 14-3-3 proteins and FKHRL1's retention in the cytoplasm. Survival factor withdrawal leads to FKHRL1 dephosphorylation, nuclear translocation, and target gene activation. Within the nucleus, FKHRL1 triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene.

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Topics: PI3K/AKT/mTOR pathway (63%), AKT1 (63%), Protein kinase B (62%) ...read more

6,219 Citations


Open accessJournal ArticleDOI: 10.1016/J.CELL.2012.03.017
Mathieu Laplante1, David M. Sabatini1Institutions (1)
13 Apr 2012-Cell
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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Topics: RPTOR (67%), PI3K/AKT/mTOR pathway (61%), mTORC2 (60%) ...read more

5,792 Citations


Open accessJournal ArticleDOI: 10.1016/S0092-8674(00)80405-5
Sandeep Robert Datta1, Henryk Dudek1, Xu Tao1, Shane C. Masters2  +3 moreInstitutions (2)
17 Oct 1997-Cell
Abstract: Growth factors can promote cell survival by activating the phosphatidylinositide-3′-OH kinase and its downstream target, the serine-threonine kinase Akt. However, the mechanism by which Akt functions to promote survival is not understood. We show that growth factor activation of the PI3′K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates BAD in vitro and in vivo, and blocks the BAD-induced death of primary neurons in a site-specific manner. These findings define a mechanism by which growth factors directly inactivate a critical component of the cell-intrinsic death machinery.

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Topics: PI3K/AKT/mTOR pathway (64%), Protein kinase B (64%), Akt/PKB signaling pathway (61%) ...read more

5,721 Citations


Open access
Mathieu Laplante1, David M. Sabatini1Institutions (1)
01 Apr 2012-
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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5,671 Citations


Journal ArticleDOI: 10.1038/NRC839
Igor Vivanco1, Charles L. Sawyers1Institutions (1)
Abstract: One signal that is overactivated in a wide range of tumour types is the production of a phospholipid, phosphatidylinositol (3,4,5) trisphosphate, by phosphatidylinositol 3-kinase (PI3K) This lipid and the protein kinase that is activated by it — AKT — trigger a cascade of responses, from cell growth and proliferation to survival and motility, that drive tumour progression Small-molecule therapeutics that block PI3K signalling might deal a severe blow to cancer cells by blocking many aspects of the tumour-cell phenotype

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5,421 Citations


Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202256
20214,641
20204,641
20194,584
20184,010
20173,840

Top Attributes

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Topic's top 5 most impactful authors

Gordon B. Mills

126 papers, 19.2K citations

James A. McCubrey

122 papers, 12.9K citations

David M. Sabatini

71 papers, 40K citations

Lewis C. Cantley

67 papers, 32K citations

Alberto M. Martelli

51 papers, 4.3K citations

Network Information
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Apoptosis

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