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PI3K: Downstream AKTion Blocks Apoptosis

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TLDR
Results from Evan and colleagues demonstrated that mutants of V12 Ras that selectively stimulate PI3K and Akt/PKB but not the Raf/MEK/MAPK pathway are able to prevent c-myc-induced cell death in Rat-1 cells and granule neurons.
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This article is published in Cell.The article was published on 1997-02-21 and is currently open access. It has received 1685 citations till now. The article focuses on the topics: PI3K/AKT/mTOR pathway & Protein kinase B.

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Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation

TL;DR: It is demonstrated that the serine/threonine protein kinase Akt/PKB mediates the activation of eNOS, leading to increased NO production, and represents a novel Ca2+-independent regulatory mechanism for activation ofeNOS.
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Regulation of endothelium-derived nitric oxide production by the protein kinase Akt.

TL;DR: It is shown that the serine/threonine protein kinase Akt (protein kinase B) can directly phosphorylate eNOS on serine 1179 and activate the enzyme, leading to NO production, whereas mutant eN OS (S1179A) is resistant to phosphorylation and activation by Akt.
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Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt

TL;DR: The proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway, and active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3.
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eIF4 Initiation Factors: Effectors of mRNA Recruitment to Ribosomes and Regulators of Translation

TL;DR: The recent determination of the structure of eIF4E at atomic resolution has provided insight about how translation is initiated and regulated and suggests that eif4F is also implicated in malignancy and apoptosis.
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New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway

TL;DR: A series of publications over the past year now suggest a mechanism by which PTEN loss of function results in tumors, and PTEN appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell growth and survival by dephosphorylating the 3 position ofosphoinositides.
References
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Journal ArticleDOI

Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.

TL;DR: It is shown that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3, and it is demonstrated that PKB is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC).

Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15 (23):6541-6551

TL;DR: It is demonstrated that activation of PKBalpha by insulin or insulin‐like growth factor‐1 (IGF‐1) results from phosphorylation of both Thr308 and Ser473, that phosphorylate of both residues is critical to generate a high level of P KBalpha activity and that the phosphorylated of Thr308 in vivo is not dependent on phosphorylations of Ser473 or vice versa.
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Mechanism of activation of protein kinase B by insulin and IGF-1.

TL;DR: In this paper, the activation of PKBalpha was accompanied by its phosphorylation at Thr308 and Ser473 and, like activation, likeactivation was prevented by the phosphatidylinositol 3-kinase inhibitor wortmannin.
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Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction

TL;DR: A role for PKB in PI(3)K-mediated signal transduction is suggested and a constructed Gag–PKB fusion protein, homologous to the v-akt oncogene, displays significantly increased ligand-independent kinase activity.
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