Article

AKT/PKB signaling: navigating downstream. Cell

Department of Genetics and Complex Diseases, Harvard School of Public Health, SPH2-117, Boston, MA 02115, USA.
Cell (Impact Factor: 32.24). 07/2007; 129(7):1261-74. DOI: 10.1016/j.cell.2007.06.009
Source: PubMed

ABSTRACT

The serine/threonine kinase Akt, also known as protein kinase B (PKB), is a central node in cell signaling downstream of growth factors, cytokines, and other cellular stimuli. Aberrant loss or gain of Akt activation underlies the pathophysiological properties of a variety of complex diseases, including type-2 diabetes and cancer. Here, we review the molecular properties of Akt and the approaches used to characterize its true cellular targets. In addition, we discuss 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.

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    • "Activation of the link PI3K → Akt/PKB by insulin for the implee mentation of its metabolic effects was studied in quite a number of works171819 Signaling pathway PI3K → PKB → eNOS → sGC → PKG → CD38 → RyR attracted particular attention after revealing the activation of NO synthase by PKB [12, 13] and the participation of NO and PKG in Ca 2+ response regulation [14]. PKB/Akt is an important center in metabolic signaling processes affected by insulin, which controls cell growth, survival, prolifee ration, migration, and metabolism20212223. Isoform PKB/Akt2B functions in white fat adipocytes. "

    Full-text · Article · Feb 2016 · Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology
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    • "AKT exerts many biological effects through its key downstream effector, the mTOR complex 1 (mTORC1) [8]. mTORC1 activates two distinct downstream signaling: p70S6K and 4EBP1. "
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    ABSTRACT: Background & aims: Activating mutations of PIK3CA occur in various tumor types, including human hepatocellular carcinoma. The mechanisms whereby PIK3CA contributes to hepatocarcinogenesis remain poorly understood. Methods: PIK3CA mutants H1047R or E545K were hydrodynamically transfected, either alone or in combination with NRasV12 or c-Met genes, in the mouse liver. Results: Overexpression of H1047R or E545K alone was able to induce AKT/mTOR signaling in the mouse liver, leading to hepatic steatosis. However, none of the mice developed liver tumors over long term. In contrast, H1047R or E545K cooperated with NRasV12 or c-Met rapidly induce liver tumor formation in mice. At the molecular level, all the tumor nodules displayed activation of AKT/mTOR and Ras/MAPK cascades. Ablation of AKT2 significantly inhibited hepatic steatosis induced by H1047R or E545K and carcinogenesis induced by H1047R/c-Met or E545K/c-Met. Furthermore, tumorigenesis induced by H1047R/c-Met was abolished in conditional Raptor knockout mice. Conclusions: In conclusion, both H1047R and E545K are able to activate the AKT/mTOR pathway. An intact AKT2/mTORC1 cascade is required for tumorigenesis induced by H1047R/c-Met or E545K/c-Met in the liver. This article is protected by copyright. All rights reserved.
    Full-text · Article · Dec 2015 · Liver international: official journal of the International Association for the Study of the Liver
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    • "Fish & Shellfish Immunology angiogenesis and migration [3] [5] [17]. Akt has been highly conserved during evolution, and its homologs have been identified in detail in both mammals and invertebrates , including Drosophila melanogaster and Caenorhabditis elegans [18]. "
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    ABSTRACT: G-protein-coupled receptors (GPCRs) are the largest class of cell-surface receptors and play crucial roles in virtually every organ system. As one of the major downstream effectors of GPCRs, Akt can acquire information from the receptors and coordinate intracellular responses for many signalling pathways, through which the serine/threonine kinase masters numerous aspects of biological processes, such as cell survival, growth, proliferation, migration, angiogenesis, and metabolism. In the present study, we have characterized the first Akt1 ortholog in mollusks using the Hong Kong oyster, Crassostrea hongkongensis (designed ChAkt1). The full-length cDNA is 2,223 bp and encodes a putative protein of 493 amino acids that contains an amino-terminal pleckstin homology (PH) domain, a central catalytic domain, and a carboxy-terminal regulatory domain. Quantitative real-time PCR analysis showed that ChAkt1 mRNA is broadly expressed in various tissues and during different stages of the oyster's embryonic and larval development. Upon exposure to two stressors (microbial infection and heat shock), the expression level of ChAkt1 mRNA increases significantly. Furthermore, ChAkt1 is located in the cytoplasm in HEK293T cells, where the over-expression of ChAkt1 regulates the transcriptional activities of NF-κB and p53 reporter genes. Taken together, our results indicate that ChAkt1 most likely plays a central role in response to various stimuli in oysters and has a particular response to microbial pathogens and high temperature.
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