Transcriptional and post-translational regulation of cell adhesion mediated by the cell adhesion molecule, selectin, on lymphocytes.

由淋巴细胞上的细胞粘附分子选择素介导的细胞粘附的转录和翻译后调节。

• 批准号: 13680732
• 负责人: KANNAGI Reiji
• 金额: $ 2.24万
• 依托单位: Aichi Cancer Center
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680732/
• 关键词: selectin; lymphocyte homing; fucosyltransferase; sulfotransferases; CD44; sialyl 6-sulfo Lewis X; sialyl Lewis X; フコシルトランスフェラーゼ; スルホトランスフェラーゼ; 細胞接着; シアリル6-スルホLe^x; シアリルLe^x; CRE; GATA-3

Conventional non-sulfated sialyl Lewis x and sialyl 6-sulfo Lewis x determinants are involved in the cell adhesion of lymphocytes. Expression of non-sulfated sialyl Lewis x is mainly regulated by fucosyltransferase VII at a transcriptional level, and transcriptional factors belonging to the CREB/ATF family as well as GATA-3, Sp1 and MZF-1 are involved in its transcriptional regulation. In addition, we showed the transcriptional factors THP-1 (Gli-2), HIF-α and HIF-α also play important roles in regulation of sialyl Lewis X expression. On the other hand, GlcNAcβ : 6-O-sulfotransferases figure heavily in the regulation of sialyl 6-sulfo Lewis x expression. Among the five known isoenzymes of GlcNAcβ: 6-O-sulfotransferases, we showed that the isoenzymes called GlcNAC6ST-1 and HEC-GlcNAC6ST are closely involved in the regulation of sialyl 6-sulfo Lewis x expression in lymphocytes. The products of GlcNAcβ: 6-O-sulfotransferases also play significant role in the regulation of cell adhesion mediated by another cell adhesion molecule, CD44, which has also been known to be involved in the routine recruitment of lymphocytes.

传统的非硫酸盐化唾液酸化Lewis x和唾液酸化6-磺酸Lewis x决定簇参与淋巴细胞的细胞黏附。非硫酸化唾液酸化Lewis x的表达主要受岩藻糖基转移酶VII在转录水平上的调控，CREB/ATF家族转录因子以及GATA-3、Sp1和MZF-1参与其转录调控。此外，我们还发现转录因子Thp-1(Gli-2)、HIF-α和HIF-α也在唾液酸化Lewis X的表达调控中发挥重要作用。另一方面，GlcNAcβ：6-O-磺酸转移酶在唾液酸基6-磺基Lewis x表达的调节中起重要作用。在已知的5种GlcNAcβ：6-O-磺基转移酶同工酶中，GlcNAC6ST-1和HEC-GlcNAC6ST与调节淋巴细胞中唾液酸基6-磺基Lewis x的表达密切相关。GlcNAcβ：6-O-磺酸转移酶的产物也在另一种细胞黏附分子CD44介导的细胞黏附调节中发挥重要作用，CD44也被认为参与了淋巴细胞的常规募集。

项目成果

Schakel, K., Kannagi, R.et al.: "6-Sulfo LacNAc, a novel carbohydrate modification of PSGL-1,defines an inflammatory type of human dendritic cells"Immunity. 17. 289-301 (2002)

Schakel, K.、Kannagi, R.等人：“6-Sulfo LacNAc，PSGL-1 的一种新型碳水化合物修饰，定义了人类树突状细胞的炎症类型”免疫。

Sekine, M., Taya, C., Kikkawa, Y., Yonekawa, H., et al.: "Regulation of mouse kidney tubular epithelial cell-specific expression of core 2 GlcNAc transferase"Eur.J.Biochem.. 268. 1129-1135 (2001)

Sekine, M.、Taya, C.、Kikkawa, Y.、Yonekawa, H.等人：“核心 2 GlcNAc 转移酶的小鼠肾小管上皮细胞特异性表达的调节”Eur.J.Biochem. 268。

Kannagi R.: "Regulatory roles of carbohydrate ligands for selectins in homing of lymphocytes"Curr.Opin.Struct.Biol.. 12. 599-608 (2002)

Kannagi R.：“淋巴细胞归巢中选择素的碳水化合物配体的调节作用”Curr.Opin.Struct.Biol.. 12. 599-608 (2002)

Kannagi R.: "In Handbook of Glycosyltransferases and Their Related Genes, Taniguchi, N., Honke, K. & Fukuda, M.(eds)"Springer-Verlag, Tokyo. 237-245 (2001)

Kannagi R.：《糖基转移酶及其相关基因手册》，Taniguchi, N., Honke, K.

Uchimura, K., et al: "Specificities of N-acetylglucosamine-6-O-sulfotransferases in relation to L-selectin ligand synthesis and tumor-associated enzyme expression"J. Biol. Chem.. 277. 3979-3984 (2002)

Uchimura, K. 等人：“N-乙酰葡糖胺-6-O-磺基转移酶与 L-选择素配体合成和肿瘤相关酶表达相关的特异性”J.