对P-选择因素的功能性糖蛋白连接体的表达克隆
D Sako1, X J Chang, K M Barone
1Genetics Institute, Small Molecule Drug Discovery Group, Cambridge, Massachusetts 02140.
Cell
|December 17, 1993
概括
研究人员发现了一种与P-选择素结合的新型蛋白质,该蛋白质对白细胞粘附至关重要. 这种P-selectin连接体需要一个特定的酶来起作用,为免疫细胞相互作用提供了新的见解.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 细胞粘附 细胞粘附
背景情况:
- P-选择因介导循环白细胞和内皮细胞之间的初始粘合相互作用.
- 了解这些相互作用是解读免疫细胞贩运和炎症反应的关键.
研究的目的:
- 为了识别和表征P-selectin的功能性联结体.
- 阐明P-选择因-连接体结合的分子要求.
主要方法:
- 从HL-60cDNA库中克隆一个P-选择素配体的表达式.
- 转染COS细胞与配体和一个fucosyltransferase.
- 使用依赖和抗体抑制试验分析P-选择因结合的分析.
- 结合体表达和可溶性结构的表征.
主要成果:
- 一种新型的素类型的跨膜蛋白被确定为一种功能性的P-选择素连接体.
- 配体和fucosyltransferase的同时表达对于显著的P-选择素结合是必要的.
- 结合是依赖的,并且可以通过抗P-选择因抗体抑制.
- 连接体形成220kDa的同位体,可溶性形式也与P-选择素结合.
结论:
- 已经确定了一种新的P-选择因子连接体,在白细胞-内皮细胞粘附中发挥着关键作用.
- 基转移酶的活性对于这种P-选择素配体的功能表达至关重要.
- 这一发现为了解选择性介导粘附和潜在的治疗点提供了分子基础.
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