Fig. 2.

AKT signaling network targets and regulates critical cellular substrates. A AKT regulation of targeted proteins in normal cells. AKT phosphorylation of downstream substrates determines regulation of distinct cellular functions. There are several AKT cytoplasmic targets, including BAD, IKKα, FOXO, MDM2, CHK1, p21, p27, GSK-3, and TSC2, representing crucial signaling nodes that interlink AKT signaling with supplementary cellular regulatory circuits. In normal conditions, PAM pathway moderately promotes essential cellular functions such as survival, proliferation, growth and metabolism. B AKT regulation of targeted proteins in cancer cells. Mutations in RTK, Ras, PI3K, PTEN protein phosphatase, AKT, and/or other proto-oncogenes, may occur, resulting in AKT overexpression, leading to enhanced inhibition of BAD, FOXO, CHK1, p21, p27, GSK3, and TSC2, as well as increased activity of IKKα, MDM2, with consequently higher survival, increased proliferation, enhanced growth and boosted metabolism. Activation (phosphorylation or non-phosphorylation) is shown with arrowhead lines, inhibition (phosphorylation or non-phosphorylation) is indicated with blocked lines, and dephosphorylation, carried out by phosphatases, is displayed with roundhead lines. Red lightning symbol shows mutation for a particular gene in the PAM pathway. Red crosses emphasise signaling blockage, whereas green dash-dotted lines (adjacent to arrowhead lines) highlight signaling enhancement. P: phosphoryl group