Author
Nissim Hay
Other affiliations: University of California, San Francisco, University of California, Berkeley, Northwestern University ...read more
Bio: Nissim Hay is an academic researcher from University of Illinois at Chicago. The author has contributed to research in topics: Protein kinase B & PI3K/AKT/mTOR pathway. The author has an hindex of 72, co-authored 139 publications receiving 27523 citations. Previous affiliations of Nissim Hay include University of California, San Francisco & University of California, Berkeley.
Topics: Protein kinase B, PI3K/AKT/mTOR pathway, AKT1, Phosphorylation, Kinase
Papers published on a yearly basis
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TL;DR: Both the upstream components of the signaling pathway(s) that activates mammalian TOR (mTOR) and the downstream targets that affect protein synthesis are described.
Abstract: The evolutionarily conserved checkpoint protein kinase, TOR (target of rapamycin), has emerged as a major effector of cell growth and proliferation via the regulation of protein synthesis. Work in the last decade clearly demonstrates that TOR controls protein synthesis through a stunning number of downstream targets. Some of the targets are phosphorylated directly by TOR, but many are phosphorylated indirectly. In this review, we summarize some recent developments in this fast-evolving field. We describe both the upstream components of the signaling pathway(s) that activates mammalian TOR (mTOR) and the downstream targets that affect protein synthesis. We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity.
4,074 citations
TL;DR: The results suggest that uncoupling of survival and mitogenesis can be explained by differing abilities of distinct mitogens to efficiently induce the PI 3-kinase/Akt signaling pathway.
Abstract: Serum and certain growth factors have the ability to inhibit programmed cell death (apoptosis) and promote survival. The mechanism by which growth factors deliver an anti-apoptotic signal and the mechanism by which this survival signal is uncoupled from mitogenesis are not clear. We studied five downstream effectors of growth factor receptors--Ras, Raf, Src, phosphoinositide 3-kinase (PI 3-kinase), and Akt (PKB)--for their abilities to block apoptosis. Activated forms of Ras, Raf, and Src, although transforming, were not sufficient to deliver a survival signal upon serum withdrawal. In contrast, inhibition of PI 3-kinase accelerated apoptosis, and an activated form of the serine/threonine kinase Akt, a downstream effector of PI 3-kinase, blocked apoptosis. The ability of Akt to promote survival was dependent on and proportional to its kinase activity. In Rat1a fibroblasts, activated Akt did not alter Bcl-2 or Bcl-X(L) expression but inhibited Ced3/ICE-like activity. Thus, the PI 3-kinase/Akt (PKB) signaling pathway transduces a survival signal that ultimately blocks Ced3/ICE-like activity. These results suggest that uncoupling of survival and mitogenesis can be explained by differing abilities of distinct mitogens to efficiently induce the PI 3-kinase/Akt signaling pathway.
1,085 citations
TL;DR: The disruption of the most ubiquitously expressed member of the akt family of genes, akt1, in the mouse is reported, resulting in viable but smaller mice and mice that are more susceptible to apoptosis induced by TNF, anti-Fas, UV irradiation, and serum withdrawal.
Abstract: The serine/threonine kinase Akt has been implicated in the control of cell survival and metabolism. Here we report the disruption of the most ubiquitously expressed member of the akt family of genes, akt1, in the mouse. Akt1−/− mice are viable but smaller when compared to wild-type littermates. In addition, the life span of Akt1−/− mice, upon exposure to genotoxic stress, is shorter. However, Akt1−/− mice do not display a diabetic phenotype. Increased spontaneous apoptosis in testes, and attenuation of spermatogenesis is observed in Akt1−/− male mice. Increased spontaneous apoptosis is also observed in the thymi of Akt1−/− mice, and Akt1−/− thymocytes are more sensitive to apoptosis induced by γ-irradiation and dexamethasone. Finally, Akt1−/− mouse embryo fibroblasts (MEFs) are more susceptible to apoptosis induced by TNF, anti-Fas, UV irradiation, and serum withdrawal.
956 citations
TL;DR: The PPP plays a pivotal role in helping glycolytic cancer cells to meet their anabolic demands and combat oxidative stress, and its importance in cancer cell metabolism and survival is summarized.
948 citations
TL;DR: The serine/threonine kinase Akt, or protein kinase B (PKB), has recently been a focus of intense research and suggests that Akt/PKB is a critical factor in the genesis of cancer.
936 citations
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TL;DR: The author regrets the lack of citations for many important observations mentioned in the text, but their omission is made necessary by restrictions in the preparation of review manuscripts.
7,653 citations
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.
6,481 citations
TL;DR: It is shown 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.
5,831 citations
TL;DR: Small-molecule therapeutics that block PI3K signalling might deal a severe blow to cancer cells by blocking many aspects of the tumour-cell phenotype.
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
5,654 citations
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.
5,553 citations