Drosophila PI3 kinase and Akt involved in insulin-stimulated proliferation and ERK pathway activation in Schneider cells

• Published in: Cellular signalling Vol. 16; no. 11; pp. 1309 - 1317
• Main Authors: Kim, Sung-Eun, Cho, Jae-Young, Kim, Kyung-Sup, Lee, Su-Jae, Lee, Ki-Hoo, Choi, Kang-Yell
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.11.2004
• Subjects: AKT; Animals; Cell Cycle - drug effects; Cell Cycle - physiology; Cell Line; Cell proliferation; Cell Proliferation - drug effects; Drosophila; Drosophila melanogaster; Drosophila Proteins; Enzyme Inhibitors - pharmacology; Extracellular Signal-Regulated MAP Kinases - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; G1 Phase - drug effects; G1 Phase - physiology; Insulin - metabolism; Insulin - pharmacology; Insulin pathway; MAP Kinase Kinase 1 - metabolism; Phosphatidylinositol 3-Kinases - metabolism; PI3 kinase; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; S Phase - drug effects; S Phase - physiology; Signal Transduction - drug effects; Signal Transduction - physiology; Cell proliferation; Insulin pathway; AKT; PI3 kinase; Drosophila
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2004.04.004

We have characterized the role of Drosophila PI3K and AKT in ERK pathway activation involving insulin-induced proliferation using Drosophila Schneider cells. After insulin treatment, dPI3K and dAKT activities were both increased along with activation of the dERK pathway components dMEK and dERK. The insulin-induced activations of dERK and dAKT were blocked by LY294002, dPTEN, and by an AKT inhibitor, indicating involvement of dPI3K and dAKT in the insulin-induced dERK and dAKT activations. Proliferation and the G1 to S phase cell cycle progression due to insulin were also blocked by PI3K and AKT inhibitors, indicating that the Drosophila PI3K–AKT pathway involves insulin-mediated cell proliferation. The insulin-stimulated size increase was blocked by both LY294002 and AKT inhibitor, not by U0126, indicating that insulin-mediated size control by dPI3K and dAKT occurs independently of the ERK pathway. This study indicates that dPI3K and dAKT are involved in insulin-induced ERK pathway activation leading to proliferation in Drosophila Schneider cells.