Alpha 1,3-fucosyltransferase-VII regulates the signaling molecules of the insulin receptor pathway

作者：Wang Qiu yan; Zhang Ying; Chen Hai jiao; Shen Zong hou; Chen Hui li^*

来源：FEBS Journal, 2007, 274(2): 526-538.

DOI：10.1111/j.1742-4658.2006.05599.x

• epidermal growth factor receptor
• alpha 1
• 3-fucosyltransferase-VII
• human hepatocarcinoma cell line
• insulin receptor
• signaling molecules

Two H7721 human hepatocarcinoma cell lines showing moderate and high expression of alpha 1,3-fucosyltransferase (FucT)-VII cDNA were established and designated FucTVII-M and FucTVII-H, respectively. In alpha 1,3-FucT-VII-transfected cells, expression of insulin receptor (InR) alpha- and beta subunits and epidermal growth factor receptor (EGFR) on the cell surface and in cells, as well as the sialyl Lewis X (SLe(x), the product of alpha 1,3-FucT-VII) content of the EGFR were unchanged. However the level of SLe(x) on the InR alpha subunit (InR-alpha) was increased dramatically. Tyrosine autophosphorylation of InR-beta , but not EGFR, was elevated. Concomitantly, tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), Ser/Thr phosphorylation of protein kinase B (PKB; Akt), p42/44 mitogen-activated protein kinase (MAPK), MAPK kinase (MEK), and the protein of some other signaling molecules, such as phosphoinositide-dependent kinase-1 (PDK-1), novel protein kinase (PKN), c-Raf-1 and beta-catenin were also upregulated. The activities of PKB and transcription factor TCF were concomitantly stimulated. Upregulation of InR signaling molecules and their phosphorylation was correlated with the level of SLe(x) on InR-alpha and alpha 1,3-FucT-VII expression in cells. In addition, the phosphorylation intensity and difference in phosphorylation intensity between cells with different levels of alpha 1,3-FucT-VII expression were attenuated significantly by the inhibitor of InR tyrosine kinase and by the mAb to SLe(x). Furthermore, insulin-induced signaling was facilitated in alpha 1,3-FucT-VII-transfected cells, particularly FucTVII-H. These findings provide strong evidence that alpha 1,3-FucT-VII may affect insulin signaling by upregulating the phosphorylation and expression of some signaling molecules involved in the InR-signaling pathway. These effects are likely mediated by its product, SLe(x), on the glycans of the InR. This is the first study to report that changes in the terminal structure of glycans on a surface receptor can modify cell signaling.

• 出版日期2007-1
• 单位复旦大学