Voglmeir Josef, Laurent Nicolas, Flitsch Sabine L, Oelgeschläger Michael, Wilson Iain B H
Department für Chemie, Universität für Bodenkultur, Wien, Austria; Manchester Interdisciplinary Biocentre, University of Manchester, UK.
Manchester Interdisciplinary Biocentre, University of Manchester, UK.
Comp Biochem Physiol B Biochem Mol Biol. 2015 Feb;180:40-7. doi: 10.1016/j.cbpb.2014.10.003. Epub 2014 Oct 23.
The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. Until now, the mammalian forms of these enzymes have been the best characterized. However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis. In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-β/BMP signaling. In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo.
动物中粘蛋白型O-连接聚糖的生物合成由多肽N-乙酰半乳糖胺基转移酶（GalNAc-Ts）大家族的成员启动，这些酶在胚胎发生、器官发生、成体组织稳态和致癌作用中发挥重要作用。到目前为止，这些酶的哺乳动物形式已得到最充分的表征。然而，来自非洲爪蟾（非洲爪蟾）的两种N-乙酰半乳糖胺基转移酶（xGalNAc-T6和xGalNAc-T16），它们与人类GALNT6和GALNT16（GALNTL1）基因编码的酶最同源，在胚胎发生中的TGF-β/BMP信号传导中显示出相反的作用。在本研究中，我们进一步研究了这两种酶，并通过原位杂交和过表达实验证明了它们在非洲爪蟾胚胎发生过程中的体内功能存在差异。就酶活性而言，发现这两种酶对EA2肽均有活性，但对基于ActR-IIB序列的肽显示出不同的活性，ActR-IIB是一种与TGF-β/BMP信号传导相关的受体。总之，这些数据表明，来自N-乙酰半乳糖胺基转移酶不同分支的这两种酶不仅表现出不同的底物特异性，而且在体内具有特定且独特的表达模式和生物学活性。
