Xuan Nguyen Truong Le, Choi Joung Woo, Lee Sang Bae, Ye Keqiang, Woo Soo-Dong, Lee Kyung-Hoon, Ahn Jee-Yin
Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
Biochem Biophys Res Commun. 2006 Oct 20;349(2):789-98. doi: 10.1016/j.bbrc.2006.08.120. Epub 2006 Aug 28.
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.
神经生长因子（NGF）促使Akt转位至细胞核，在细胞核中它使核内靶点发生磷酸化。在此，我们描述了Akt磷酸化可促进Akt的核转位，并且是其核内滞留所必需的。Akt-K179A、T308A、S473A突变体的过表达未能显示出核转位或核内Akt磷酸化，而野生型对应物的表达在NGF刺激下引发了显著的Akt磷酸化并诱导了核转位。使用PI3K抑制剂和多种PI3K突变体，我们表明Akt的核转位是由PI3K的激活介导的，并且细胞核内的Akt磷酸化状态需要PI3K活性。因此，PI3K的活性可能有助于Akt的核转位，并且在NGF刺激条件下，Akt磷酸化对于其核内滞留至关重要。
