AKT/PKB Signaling: Navigating the Network
#MMPMID28431241
Manning BD
; Toker A
Cell
2017[Apr]; 169
(3
): 381-405
PMID28431241
show ga
The Ser and 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.
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