Insulin rapidly induces nuclear translocation of PI3-kinase in HepG2 cells.
Insulin action on nuclear PI3-Kinase and IRS-1 was explored in HepG2 cells. Following insulin treatment, the cells were subjected to subcellular fractionation. Western blot analyses were carried out to identify IRS-1 and PI3-Kinase in the nuclear and postnuclear preparations. IRS-1 protein was identified in the nucleus under basal condition. Insulin had no effect in the content of nuclear IRS-1. In contrast, PI3-Kinase was not detected under basal condition. However, insulin treatment for 1 to 10 min caused significant increase of PI3-Kinase in the nucleus while it induced corresponding decrease of PI3-Kinase in cytoplasm. Strikingly, Insulin stimulated the association of IRS-1 and PI3-Kinase in the nucleus in a similar kinetics with the nuclear translocation of PI3-Kinase. These results suggest that insulin induces nuclear translocation of PI3-Kinase and the translocated PI3-Kinase associates with nuclear IRS-1. The association of IRS-1 and PI3-Kinase in the nucleus in response to insulin may play important roles in nuclear insulin actions.
Kim
S J
SJ
Department of Pharmacology, School of Dentistry Kyung-Hee University, Seoul, Korea. kimsj@nms.kyunghee.ac.kr
D015153:Blotting, Western; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007700:Kinetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin