A role for the epidermal growth factor-like domain of P-selectin in ligand recognition and cell adhesion.
A role for the epidermal growth factor-like domain of P-selectin in ligand recognition and cell adhesion.
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DOI：
10.1083/jcb.124.4.609
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发表时间：
1994-02
期刊：
影响因子：
--
通讯作者：
Tedder TF
中科院分区：
文献类型：
--
作者：
Kansas GS;Saunders KB;Ley K;Zakrzewicz A;Gibson RM;Furie BC;Furie B;Tedder TF
粘附分子的选择素家族介导白细胞与内皮细胞的初始相互作用。每个选择素的胞外区含有氨基末端C型凝集素结构域，随后是EGF样结构域和多个短的共有重复单元（SCR）。先前的研究间接地表明了选择素的每个胞外结构域在细胞粘附中的作用。在这项研究中，通过L-和P-选择素之间的结构域交换产生的一组嵌合选择素被用来直接检查细胞外结构域在细胞粘附中的作用。L-和P-选择素之间仅交换凝集素结构域赋予母体分子凝集素结构域的粘附和配体识别功能。然而，含有L-选择素的凝集素结构域和P-选择素的EGF样结构域的嵌合选择素表现出双重配体结合特异性。这些嵌合蛋白支持粘附骨髓细胞和高内皮微静脉（HEV）的淋巴结和肠系膜微静脉在体内。SCR结构域的交换对受体功能或特异性没有可检测的影响。因此，P-选择素的EGF样结构域可能在P-选择素介导的配体识别和白细胞粘附中起直接作用，凝集素加上EGF样结构域共同形成功能性配体识别单元。
The selectin family of adhesion molecules mediates the initial interactions of leukocytes with endothelium. The extracellular region of each selectin contains an amino-terminal C-type lectin domain, followed by an EGF-like domain and multiple short consensus repeat units (SCR). Previous studies have indirectly suggested a role for each of the extracellular domains of the selectins in cell adhesion. In this study, a panel of chimeric selectins created by exchange of domains between L- and P-selectin was used to directly examine the role of the extracellular domains in cell adhesion. Exchange of only the lectin domains between L- and P-selectin conferred the adhesive and ligand recognition functions of the lectin domain of the parent molecule. However, chimeric selectins which contained both the lectin domain of L- selectin and the EGF-like domain of P-selectin exhibited dual ligand- binding specificity. These chimeric proteins supported adhesion both to myeloid cells and to high endothelial venules (HEV) of lymph nodes and mesenteric venules in vivo. Exchange of the SCR domains had no detectable effect on receptor function or specificity. Thus, the EGF- like domain of P-selectin may play a direct role in ligand recognition and leukocyte adhesion mediated by P-selectin, with the lectin plus EGF- like domains collectively forming a functional ligand recognition unit.