title: Akt phosphorylation is essential for nuclear translocation and retention in NGF-stimulated PC12 cells.
abstract: Nerve growth factor (NGF) elicits Akt translocation into the nucleus, where it phosphorylates nuclear targets. Here, we describe that Akt phosphorylation can promote the nuclear translocation of Akt and is necessary for its nuclear retention. Overexpression of Akt-K179A, T308A, S473A-mutant failed to show either nuclear translocation or nuclear Akt phosphorylation, whereas expression of wild-type counterpart elicited profound Akt phosphorylation and induced nuclear translocation under NGF stimulation. Employing the PI3K inhibitor and a variety of mutants PI3K, we showed that nuclear translocation of Akt was mediated by activation of PI3K, and Akt phosphorylation status in the nucleus required PI3K activity. Thus the activity of PI3K might contribute to the nuclear translocation of Akt, and that Akt phosphorylation is essential for its nuclear retention under NGF stimulation conditions.
authors.affiliation: Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
authors.forename: Truong Le
authors.initials: TL
authors.lastname: Xuan Nguyen
authors.forename: Joung Woo
authors.initials: JW
authors.lastname: Choi
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Lee
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
authors.forename: Soo-Dong
authors.initials: SD
authors.lastname: Woo
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Lee
authors.forename: Jee-Yin
authors.initials: JY
authors.lastname: Ahn
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D004789:Enzyme Activation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D009154:Mutation; D020932:Nerve Growth Factor / Q000378:metabolism*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt