PTEN expression responds to transcription factor POU and regulates p-AKT levels during diapause initiation in the cotton bollworm, Helicoverpa armigera.

Diapause is a complex physiological response accompanied by many signaling pathways participating in the process. Previous studies have shown that p-AKT levels in brains of diapause-destined pupae are elevated by ROS, and the activated AKT promotes Glut expression for glucose uptake during diapause entry in Helicoverpa armigera. However, the mechanism by which ROS activate AKT is still unclear. Here, we show that PTEN, a PI3K/p-AKT signaling inhibitor, was significantly lower in the brains of diapause-destined pupae and that p-AKT levels were elevated by a lack of PTEN dephosphorylating PIP3. In addition, POU was identified as a transcription factor that binds to the PTEN promoter and regulates its expression. POU expression was enhanced by ecdysone but suppressed by ROS, suggesting that POU/PTEN plays a central role in responding to ROS signaling and regulating p-AKT levels. These results suggest that ecdysone and ROS participate together in the regulation of insect diapause through downregulation of POU/PTEN, which elevates p-AKT levels.

TGF-ß signaling regulates p-Akt levels via PP2A during diapause entry in the cotton bollworm, Helicoverpa armigera.

Akt, which is a key kinase in the insulin signaling pathway, plays important roles in glucose metabolism, cell proliferation, transcription and cell migration. Our previous studies indicated that low insulin levels and high p-Akt levels are present in diapause-destined individuals. Here, we show that PI3K, which is upstream of Akt, is low in diapause-destined pupal brains but high in p-Akt levels, implying that p-Akt is modified by factors other than the insulin signaling pathway. Protein phosphatase 2A (PP2A), which is a key regulator in the TGF-ß signaling pathway, can directly bind to and dephosphorylate Akt. Low PP2A expression and activity in diapause-destined individuals suggest that a weak Akt dephosphorylation contributes to p-Akt accumulation. In addition, transforming growth factor-ß receptor I (TßRI), which is upstream of PP2A, increases the activity of PP2A and decreases the p-Akt levels. These results show that TGF-ß signaling decreases p-Akt levels by increasing the activity of PP2A. This is the first report showing that TGF-ß signaling negatively regulates the insulin pathway in insect development or diapause.