Trigwell S, Wood L, Jones P
School of Biomedical Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, United Kingdom.
Biochem Biophys Res Commun. 2000 Nov 19;278(2):440-6. doi: 10.1006/bbrc.2000.3818.
The urokinase plasminogen activator receptor (uPAR) plays an important role in the migration of leukocytes. It occurs as a membrane-bound form that contains a glycosylphosphatidylinositol (GPI) anchor and also as a soluble form (suPAR) that lacks the GPI anchor. Recently, a sequence of amino acids, SRSRYLE, within the receptor has been found to become unmasked on uPA binding or chymotrypsin cleavage. Exposure of the epitope results in the activation of p56/p59(hck) kinase and chemotaxis of myelomonocytic cells. Using an epitope-tagged suPAR molecule, we found that both three-domain and two-domain suPAR promote the adhesion of differentiated THP-1 cells to fibronectin and vitronectin, indicating that suPAR can modify cell adhesion as well as cell migration. In addition, we found that the amino acid sequence RYLE, within the chemotactic peptide, is conserved across species and that alanine substitution of Tyr 92 decreased the ability of the peptide to activate p56/59(hck).
尿激酶型纤溶酶原激活物受体（uPAR）在白细胞迁移中起重要作用。它以含有糖基磷脂酰肌醇（GPI）锚定的膜结合形式存在，也以缺乏GPI锚定的可溶性形式（suPAR）存在。最近，已发现该受体中的一段氨基酸序列SRSRYLE在uPA结合或胰凝乳蛋白酶切割时会暴露出来。表位的暴露导致p56/p59（hck）激酶的激活和骨髓单核细胞的趋化作用。使用表位标记的suPAR分子，我们发现三结构域和两结构域的suPAR均能促进分化的THP-1细胞与纤连蛋白和玻连蛋白的黏附，这表明suPAR既能调节细胞迁移，也能改变细胞黏附。此外，我们发现趋化肽中的氨基酸序列RYLE在物种间是保守的，并且Tyr 92的丙氨酸替代降低了该肽激活p56/59（hck）的能力。
