Soluble urokinase receptor promotes cell adhesion and requires tyrosine-92 for activation of p56/59(hck).

Soluble urokinase receptor promotes cell adhesion and requires tyrosine-92 for activation of p56/59(hck).
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可溶性尿激酶受体促进细胞粘附,并需要 tyrosine-92 来激活 p56/59(hck)。

DOI:
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发表时间:
2000
期刊:
Biochemical and Biophysical Research Communications - BBRC
影响因子:
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通讯作者:
P. Jones
P. Jones
中科院分区:
--
文献类型:
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作者:
S. Trigwell;L. Wood;P. Jones

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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)锚的膜结合形式存在,也以缺乏GPI锚的可溶形式(suPAR)存在。最近,已发现受体内的氨基酸序列SRSRYLE在uPA结合或胰凝乳蛋白酶切割时变得暴露。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性。使用表位标记的suPAR分子,我们发现,三结构域和两个结构域的suPAR促进分化的THP-1细胞与纤连蛋白和玻连蛋白的粘附,表明suPAR可以修改细胞粘附以及细胞迁移。此外,我们发现趋化肽内的氨基酸序列RYLE在物种间是保守的,并且Tyr 92的丙氨酸取代降低了肽激活p56/59(hck)的能力。
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).
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