在用PUGNAc和胰岛素样生长因子-1处理后，Akt1会被O-连接的N-乙酰葡糖胺动态修饰。

Akt1 is dynamically modified with O-GlcNAc following treatments with PUGNAc and insulin-like growth factor-1.

作者信息

Gandy Johanna C, Rountree Abigail E, Bijur Gautam N

机构信息

Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Sparks Center, Room 1009, Birmingham, AL 35294-0017, USA.

出版信息

FEBS Lett. 2006 May 29;580(13):3051-8. doi: 10.1016/j.febslet.2006.04.051. Epub 2006 Apr 27.

DOI:10.1016/j.febslet.2006.04.051

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2493066/

Abstract

The Ser/Thr kinase Akt1 is activated by growth factors subsequent to its phosphorylation on Thr308 and Ser473. In the present study, Akt1 was found to be constitutively modified with O-GlcNAc. Treatment of SH-SY5Y cells with O(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), which inhibits the enzymatic removal of O-GlcNAc from proteins, increased cytosolic O-GlcNAc-Akt1 levels. Treatment of cells with insulin-like growth factor-1 (IGF-1) also increased O-GlcNAc-Akt1 levels and increased Akt1 phosphorylation. PUGNAc treatment did not attenuate IGF-1 induced Akt1 phosphorylation. These results indicate that Akt1 can be simultaneously modified with O-GlcNAc and phosphorylated. However, PUGNAc induced the nuclear accumulation of Akt1 suggesting that the O-GlcNAc-modification on Akt1 may play a role in Akt1 nuclear localization.

摘要

丝氨酸/苏氨酸激酶Akt1在苏氨酸308和丝氨酸473磷酸化后被生长因子激活。在本研究中，发现Akt1持续被O-连接的N-乙酰葡糖胺（O-GlcNAc）修饰。用O（2-乙酰氨基-2-脱氧-D-吡喃葡萄糖亚基）氨基-N-苯基氨基甲酸酯（PUGNAc）处理SH-SY5Y细胞，该物质可抑制从蛋白质上去除O-GlcNAc的酶促反应，从而增加了胞质中O-GlcNAc-Akt1的水平。用胰岛素样生长因子-1（IGF-1）处理细胞也增加了O-GlcNAc-Akt1的水平并增加了Akt1的磷酸化。PUGNAc处理并未减弱IGF-1诱导的Akt1磷酸化。这些结果表明Akt1可同时被O-GlcNAc修饰并磷酸化。然而，PUGNAc诱导了Akt1的核内积累，提示Akt1上的O-GlcNAc修饰可能在Akt1的核定位中起作用。