AKT/PKB Signaling: Navigating Downstream

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.

Lipid signalling in disease

“…3; for reviews see REFS 35,36). PKB/Akt is upregulated or mutated in some tumours, and a mutation in the phosphoinositide-binding domain of PKB /Akt1 that causes it to associate with the plasma membrane and renders it constitutively active has been identified 37 .…”

The ubiquitin-like modifier FAT10 in cancer development

“…The serine/threonine kinase Akt (or PKB) is a central node in cell signaling downstream of cytokines, growth factors and other stimuli. Akt signaling plays a role in regulating cell survival, differentiation, proliferation and angiogenesis, pointing to a role of the Akt signaling pathway in carcinogenesis (Manning and Cantley, 2007). One of the downstream targets of Akt is GSK3␤, which is inactivated when getting phosphorylated by Akt, and signal transduction via Akt/GSK3␤ was shown to promote TNF-␣-mediated epithelial-mesenchymal transition (EMT) (Wang et al, 2013).…”

The transcriptional induction of PIK3CA in tumor cells is dependent on the oncoprotein Y-box binding protein-1

“…The importance of PI3K signaling in cancer is unquestionable, as increased PI3K activity has been observed in many different cancer types and believed to be one of the driving forces behind tumorigenesis (Manning and Cantley, 2007). Previous studies of knockout mice have demonstrated that an imbalance in the levels of the p110 catalytic and p85 regulatory subunits suffices to affect PI3K activity significantly (Ueki et al, 2002).…”