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Journal ArticleDOI

Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt

TLDR
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.
Abstract
BAD is a distant member of the Bcl-2 family that promotes cell death. Phosphorylation of BAD prevents this. BAD phosphorylation induced by interleukin-3 (IL-3) was inhibited by specific inhibitors of phosphoinositide 3-kinase (PI 3-kinase). Akt, a survival-promoting serine-threonine protein kinase, was activated by IL-3 in a PI 3-kinase-dependent manner. 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. Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway.

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Journal ArticleDOI

Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor

TL;DR: It is demonstrated that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors, which triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene.
Journal ArticleDOI

AKT/PKB signaling: navigating downstream.

TL;DR: Those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration are discussed.
Journal ArticleDOI

The Bcl-2 Protein Family: Arbiters of Cell Survival

TL;DR: Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens.
Journal ArticleDOI

Cellular survival: a play in three Akts

TL;DR: The mechanisms by which survival factors regulate the PI3K/c-Akt cascade, the evidence that activation of the PI 3K/ c-AKT pathway promotes cell survival, and the current spectrum of c- akt targets and their roles in mediating c- Akt-dependent cell survival are reviewed.
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BCL-2 family members and the mitochondria in apoptosis

TL;DR: As the BCL-2 family members reside upstream of irreversible cellular damage and focus much of their efforts at the level of mitochondria, they play a pivotal role in deciding whether a cell will live or die, and it is argued that the amphipathic a-helical BH3 domain serves as a critical death domain in the pro-apoptotic members.
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).
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Apoptosis by death factor.

TL;DR: This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture of Japan and by a Research Grant from the Princess Takamatsu Cancer Research Fund, and performed in part through Special Coordination Funds of the Science and Technology Agency of the Japanese Government.
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Programmed Cell Death in Animal Development

TL;DR: Because of the limited number of references allowed, the authors were unable to cite many important papers; they apologize to their authors.
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Social controls on cell survival and cell death

TL;DR: For some mammalian cells, programmed death seems to occur by default unless suppressed by signals from other cells, so dependence on specific survival signals provides a simple way to eliminate misplaced cells, for regulating cell numbers and, perhaps, for selecting the fittest cells.
Journal ArticleDOI

Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces bax and promotes cell death

TL;DR: A novel interacting protein, Bad, whose homology to Bcl-2 is limited to the BH1 and BH2 domains is identified, whose role in the mammalian cell death pathway is determined by these competing dimerizations in which levels of Bad influence the effectiveness of BCl-2 versus B cl-xL in repressing death.
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