Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells.
Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells.
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发表时间：
1999-02
影响因子：
4
通讯作者：
D. Nath;P. Slocombe;P. Stephens;A. Warn;G. Hutchinson;K. Yamada;A. Docherty;G. Murphy
中科院分区：
文献类型：
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作者：
D. Nath;P. Slocombe;P. Stephens;A. Warn;G. Hutchinson;K. Yamada;A. Docherty;G. Murphy
Metargidin(ADAM-15)是一种属于ADAM家族的I型跨膜糖蛋白，广泛表达于不同组织和细胞中。该家族的成员包括一个氨基末端的金属蛋白酶结构域，然后是一个去整合素结构域、一个富含半胱氨酸的区域和一个膜近端的EGF样结构域。Metargidin的去整合素结构域包含一个RGD三肽序列，这表明它可能与整合素蛋白家族相互作用。在这里，我们通过使用一种含有Metargidin胞外区的嵌合蛋白与人免疫球蛋白的Fc部分融合，在造血细胞上鉴定Metargidin的整合素配体。通过固相细胞粘附法分析与一组人类细胞株的结合活性。Metargidin以特定的方式与单核细胞系U937和T细胞系MOLT-4结合。粘附性依赖于二价阳离子和温度，并被Mn2+强烈增强，所有这些特征都是整合素介导的结合。利用一组抗整合素抗体，我们发现Alphavbeta3是U937细胞上Metargidin的配体。相反，对于MOLT-4细胞，整合素α5beta1有助于细胞结合。当基于RGD的多肽抑制细胞与两种细胞系的结合时，黏附是由Metargidin的去整合素域介导的。用纯化的重组整合素进行固相黏附实验进一步证实了αvbeta3和alpha5beta1与metargidin相互作用的特异性。这些结果表明，Metargidin可以通过与alphavbeta3和alpha5beta1整合素相互作用而发挥细胞黏附分子的作用。
Metargidin (ADAM-15) is a type I transmembrane glycoprotein belonging to the ADAM (A Disintegrin and Metalloprotease Domain) family of proteins and is widely expressed in different tissues and cell types. Members of this family contain an amino-terminal metalloprotease domain followed by a disintegrin domain, a cysteine-rich region and a membrane proximal EGF-like domain. The disintegrin domain of metargidin contains an RGD tripeptide sequence, suggesting that it may potentially interact with the integrin family of proteins. Here we identify integrin ligands for metargidin on haemopoietic cells, by using a chimeric protein containing the extracellular domain of metargidin fused to the Fc portion of human IgG. Binding activity to a panel of human cell lines was analysed by solid-phase cell-adhesion assays. Metargidin bound to a monocytic cell line, U937, and a T cell line, MOLT-4, in a specific manner. Adhesion was divalent cation- and temperature- dependent and strongly enhanced by Mn2+, all features of integrin-mediated binding. Using a panel of anti-integrin antibodies we show that alphavbeta3 is a ligand for metargidin on U937 cells. In contrast, for MOLT-4 cells, the integrin alpha5beta1 contributes to cell binding. Adhesion was mediated by the disintegrin domain of metargidin as RGD-based peptides inhibited cell binding to both cell lines. The specificity of the interaction between both alphavbeta3 and alpha5beta1 and metargidin was further confirmed by solid-phase adhesion assays using purified recombinant integrins. These results together indicate that metargidin can function as a cell adhesion molecule via interactions with alphavbeta3 and alpha5beta1 integrins.