PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review).

The purpose of this review is to summarize the research progress of PI3K/Akt signaling pathway in erythropoiesis and glycolysis. Phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K) is activated by numerous genes and leads to protein kinase B (Akt) binding to the cell membrane, with the help of phosphoinositide‑dependent kinase, in the PI3K/Akt signal transduction pathway. Threonine and serine phosphorylation contribute to Akt translocation from the cytoplasm to the nucleus and further mediates enzymatic biological effects, including those involved in cell proliferation, apoptosis inhibition, cell migration, vesicle transport and cell cancerous transformation. As a key downstream protein of the PI3K/Akt signaling pathway, hypoxia‑inducible factor (HIF)‑1 is closely associated with the concentration of oxygen in the environment. Maintaining stable levels of HIF‑1 protein is critical under normoxic conditions; however, HIF‑1 levels quickly increase under hypoxic conditions. HIF‑1α is involved in the acute hypoxic response associated with erythropoietin, whereas HIF‑2α is associated with the response to chronic hypoxia. Furthermore, PI3K/Akt can reduce the synthesis of glycogen and increase glycolysis. Inhibition of glycogen synthase kinase 3β activity by phosphorylation of its N‑terminal serine increases accumulation of cyclin D1, which promotes the cell cycle and improves cell proliferation through the PI3K/Akt signaling pathway. The PI3K/Akt signaling pathway is closely associated with a variety of enzymatic biological effects and glucose metabolism.