Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes.

Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes.
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通过人白细胞上碳水化合物配体的唾液酸部分的环化来调节选择素结合活性。

DOI:
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发表时间:
1999
影响因子:
11.1
通讯作者:
R. Kannagi
R. Kannagi
中科院分区:
综合性期刊1区
文献类型:
--
作者:
C. Mitsuoka;K. Ohmori;N. Kimura;A. Kanamori;S. Komba;H. Ishida;M. Kiso;R. Kannagi

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我们在此提供的证据支持在人白细胞中存在选择素配体碳水化合物的生物学休眠形式,即含有修饰唾液酸的唾液酸基6-磺基刘易斯X。唾液酸的修饰包括首先通过普遍存在的去N-乙酰化/再N-乙酰化循环使唾液酸部分去N-乙酰化,然后去N-乙酰基唾液酸脱水环化形成“环状唾液酸”。“参与脱N-乙酰基唾液酸脱水的酶是一种钙依赖性酶,具有中性-碱性pH最佳值。去-N-乙酰基唾液酸6-磺基刘易斯X保留了选择素结合活性以及亲本唾液酸6-磺基刘易斯X,但环状唾液酸6-磺基刘易斯X缺乏选择素结合活性。携带环状唾液酸的唾液酸基6-磺基刘易斯X被新生成的mAb G159特异性识别。该决定簇广泛分布于正常人白细胞中,尤其是单核细胞和淋巴细胞亚群,包括NK细胞、辅助记忆T细胞、Tcr-γ δ T细胞和部分B细胞。该决定簇也被检测到在几个培养的淋巴细胞白血病细胞系和O-十四烷酰佛波醇13-乙酸酯激活的淋巴样细胞。环唾液酸6-磺基刘易斯X通过部分膜结合的钙依赖性酶(暂时称为“唾液酸环化酶”)的作用有效地形成,并且该反应的可能生理意义可能是细胞表面的选择素结合活性的快速失活。相反,积累的细胞内环唾液酸基6-磺基刘易斯X决定簇可作为选择素配体的休眠池,其在适当的刺激下被水解并在选择素依赖性细胞粘附中变得活跃。
We provide here evidence that supports the occurrence of a biologically dormant form of selectin ligand carbohydrate, the sialyl 6-sulfo Lewis X containing modified sialic acid, in human leukocytes. The modification of sialic acid involves first de-N-acetylation of sialic acid moiety through ubiquitous de-N-acetylation/re-N-acetylation cycle, followed by the dehydrative cyclization of de-N-acetyl sialic acid to form "cyclic sialic acid." The enzyme involved in the dehydration of de-N-acetyl sialic acid is a calcium-dependent enzyme having neutral-alkaline pH optimum. De-N-acetyl sialyl 6-sulfo Lewis X retained selectin binding activity as well as parental sialyl 6-sulfo Lewis X, but cyclic sialyl 6-sulfo Lewis X was devoid of selectin binding activity. Sialyl 6-sulfo Lewis X carrying the cyclic sialic acid is specifically recognized by the newly generated mAb, G159. The determinant was distributed widely among normal human leukocytes, especially on monocytes and subsets of lymphocytes including NK cells, helper memory T cells, Tcr-gammadelta T cells, and a part of B cells. The determinant was detected also on several cultured lymphocytic leukemia cell lines and O-tetradecanoylphorbol 13-acetate-activated lymphoid cells. Cyclic sialyl 6-sulfo Lewis X is efficiently formed by the action of the partly membrane-bound calcium-dependent enzyme, tentatively called "sialic acid cyclase," and a possible physiological significance of this reaction could be a rapid inactivation of selectin binding activity at the cell surface. Conversely, the accumulated intracellular cyclic sialyl 6-sulfo Lewis X determinant may function as a dormant pool of selectin ligands, which, on appropriate stimulation, is hydrolyzed and becomes active in selectin-dependent cell adhesion.
DOI: 10.1016/s0021-9258(18)68785-x
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影响因子: --
作者:
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DOI: --
发表时间: 1998
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影响因子: --
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DOI: --
发表时间: 1990
期刊: The Journal of biological chemistry
影响因子: --
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DOI: --
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期刊: The Journal of biological chemistry
影响因子: --
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