Gu Jianguo, Taniguchi Naoyuki
Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, Japan.
Cell Adh Migr. 2008 Oct-Dec;2(4):243-5. doi: 10.4161/cam.2.4.6748. Epub 2008 Oct 5.
Glycosylation is one of the most abundant posttranslational modification reactions, and nearly half of all known proteins in eukaryotes are glycosylated. In fact, changes in oligosaccharide structure (glycan) are associated with many physiological and pathological events, including cell adhesion, migration, cell growth, cell differentiation and tumor invasion. Glycosylation reactions are catalyzed by the action of glycosyltransferases, which add sugar chains to various complex carbohydrates such as glycoproteins, glycolipids and proteoglycans. Functional glycomics, which uses sugar remodeling by glycosyltransferases, is a promising tool for the characterization of glycan functions. Here, we will focus on the positive and negative regulation of biological functions of integrins by the remodeling of N-glycans with N-acetylglucosaminyltransferase III (GnT-III) and N-acetylglucosaminyltransferase V (GnT-V), which catalyze branched N-glycan formations, bisecting GlcNAc and beta1,6 GlcNAc, respectively. Typically, integrins are modified by GnT-III, which inhibits cell migration and cancer metastasis. In contrast, integrins modified by GnT-V promote cell migration and cancer invasion.
糖基化是最丰富的翻译后修饰反应之一,真核生物中近一半的已知蛋白质都发生了糖基化。事实上,寡糖结构(聚糖)的变化与许多生理和病理事件相关,包括细胞黏附、迁移、细胞生长、细胞分化和肿瘤侵袭。糖基化反应由糖基转移酶催化,糖基转移酶将糖链添加到各种复杂碳水化合物上,如糖蛋白、糖脂和蛋白聚糖。功能糖组学利用糖基转移酶进行糖重塑,是表征聚糖功能的一种有前景的工具。在这里,我们将重点关注通过用N-乙酰葡糖胺转移酶III(GnT-III)和N-乙酰葡糖胺转移酶V(GnT-V)重塑N-聚糖对整合素生物学功能的正负调控,这两种酶分别催化分支N-聚糖的形成、平分GlcNAc和β1,6 GlcNAc。通常,整合素被GnT-III修饰,这会抑制细胞迁移和癌症转移。相反,被GnT-V修饰的整合素促进细胞迁移和癌症侵袭。