The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells.
The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells.
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DOI：
10.1083/jcb.115.2.557
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发表时间：
1991-10
影响因子：
7.8
通讯作者：
Cummings, R D
中科院分区：
文献类型：
--
作者：
Zhou, Q;Moore, K L;Smith, D F;Varki, A;McEver, R P;Cummings, R D
颗粒膜蛋白-140（GMP-140）是活化血小板和内皮细胞上髓系白细胞的可诱导受体。与其他选择素一样，GMP-140识别特定的寡糖配体。然而，关于这些配体的性质的先前数据是矛盾的。我们研究了与GMP-140使用纯化的GMP-140，细胞天然表达特定的寡糖，和细胞表达克隆的糖基转移酶的配体相互作用所需的结构特征。与相关的选择素内皮白细胞粘附分子-1（ELAM-1）一样，GMP-140识别髓样和非髓样细胞上的α（2-3）唾液酸化、α（1-3）岩藻糖基化乳糖胺聚糖，包括序列Neu 5Ac α 2-3Gal β 1-4（Fuc α 1- 3）GlcNac β-R（sialyl刘易斯x）。识别需要唾液酸，因为表达大量刘易斯x但不表达唾液酸刘易斯x的细胞不与GMP-140相互作用。尽管用α 1- 3/4岩藻糖基转移酶转染的髓样HL-60细胞和CHO细胞均表达唾液酸化刘易斯x，但GMP-140以显著更高的亲和力与HL-60细胞结合。因此，唾液酸刘易斯x四糖可能需要额外的结构修饰或特异性呈递，以使流动血液中的白细胞与活化血小板或内皮上的GMP-140快速且高亲和力地相互作用。
Granule membrane protein-140 (GMP-140) is an inducible receptor for myeloid leukocytes on activated platelets and endothelium. Like other selectins, GMP-140 recognizes specific oligosaccharide ligands. However, prior data on the nature of these ligands are contradictory. We investigated the structural features required for ligand interaction with GMP-140 using purified GMP-140, cells naturally expressing specific oligosaccharides, and cells expressing cloned glycosyltransferases. Like the related selectin endothelial leukocyte adhesion molecule-1 (ELAM-1), GMP-140 recognizes alpha(2-3)sialylated, alpha(1-3)fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells, including the sequence Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1- 3)GlcNac beta-R (sialyl Lewis x). Recognition requires sialic acid, because cells expressing large amounts of Lewis x, but not sialyl Lewis x, do not interact with GMP-140. Although sialyl Lewis x is expressed by both myeloid HL-60 cells and CHO cells transfected with an alpha 1- 3/4 fucosyltransferase, GMP-140 binds with significantly higher affinity to HL-60 cells. Thus, the sialyl Lewis x tetrasaccharide may require additional structural modifications or specific presentations in order for leukocytes in flowing blood to interact rapidly and with high affinity to GMP-140 on activated platelets or endothelium.