AKT/PKB Signaling: Navigating the Network

By B. Manning, A. Toker. Cell, 2017

3,226 citations recorded by the source corpus.

The Ser/Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of Akt, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body. Mouse and human genetic studies have also revealed physiological roles for the AKT network in nearly every organ system. Our comprehension of AKT regulation and functions is particularly important given the consequences of AKT dysfunction in diverse pathological settings, including developmental and overgrowth syndromes, cancer, cardiovascular disease, insulin resistance and type-2 diabetes, inflammatory and autoimmune disorders, and neurological disorders. There has also been much progress in developing AKT-selective small molecule inhibitors. Improved understanding of the molecular wiring of the AKT signaling network continues to make an impact that cuts across most disciplines of the biomedical sciences.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c48f132f75b8eadc240f7455786c158ecd7edc78

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Citations in the corpus

PIP4Ks Suppress Insulin Signaling through a Catalytic-Independent Mechanism (2018, neutral): “Furthermore, HeLa TKD cells displayed enhanced PI3K pathway activation, as judged by S473 phosphorylation of AKT as well as AKT-mediated phosphorylation of PRAS40 (Manning and Toker, 2017; Figures 4B and 4C).”
Role of Bruton’s tyrosine kinase in B cells and malignancies (2018, background): “Full activation of AKT requires phosphorylation at position T308, induced by 3-phosphoinositide-dependent protein kinase-1 (PDK1), and at S473, phosphorylated by mechanistic target of rapamycin (mTOR) complex 2 (See Ref [55] for an excellent review).”
The PI3K/AKT pathway in obesity and type 2 diabetes (2018, background): “Similar phosphorylation events are observed at corresponding residues in AKT2 (T309 and S474) and AKT3 (T305 and S472) [22].”
The PI3K pathway in human disease (2017, positive): “P 3 , and may promote AKT activation at endomembranes (Manning and Toker, 2017).”