MULTIPLE INTEGRINS MEDIATE CELL ATTACHMENT TO CYTOTACTIN TENASCIN
MULTIPLE INTEGRINS MEDIATE CELL ATTACHMENT TO CYTOTACTIN TENASCIN
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DOI：
10.1073/pnas.90.21.10154
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发表时间：
1993-11-01
影响因子：
11.1
通讯作者：
CROSSIN, KL
中科院分区：
文献类型：
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作者：
PRIETO, AL;EDELMAN, GM;CROSSIN, KL
为了鉴定鸡细胞趋化素 (CT) 的潜在细胞表面受体，我们表征了跨越该分子的近端纤连蛋白 (FN) III 型重复序列的重组融合蛋白支持神经胶质瘤和癌细胞系附着的能力。第三个 FN III 型重复序列包含 RGD 三肽，支持细胞附着和细胞扩散；然而，RGD 突变为 RAD 并没有导致任一活性的显着丧失。此外，含有天然突变体RVD的小鼠CT的相同重复也支持细胞附着和扩散，尽管水平较低；通过将 RVD 序列突变为 RGD，这两种活性均得到增强。利用含有 RGD 的肽和充分表征的整合素抗体进行的研究表明，细胞与第三个 FN III 型重复序列的附着是由至少两种不同的 av 亚型整合素受体介导的。其他细胞受体也可能参与细胞与 CT 的附着。例如，整合素β1亚家族的抗体部分抑制细胞与完整CT的结合，但不抑制细胞与第三个FN III型重复序列的结合。这些发现表明 CT 中的 RGD 位点能够介导细胞与整合素的附着，因此不是一个隐秘的粘附位点。他们还提出了一种可能性，即 CT 在反粘附、细胞迁移、细胞增殖和细胞分化等过程中的功能可能部分是通过与多个整合素的相互作用介导的。
To identify potential cell surface receptors for chicken cytotactin (CT), we have characterized the ability of recombinant fusion proteins spanning the proximal fibronectin (FN) type III repeats of the molecule to support attachment of glioma and carcinoma cell lines. The third FN type III repeat, which contains the RGD tripeptide, supported cell attachment and cell spreading; however, mutation of RGD to RAD did not result in significant loss of either activity. In addition, the same repeat of mouse CT, which contains a natural mutant, RVD, also supported cell attachment and spreading, although at a lower level; both activities were increased by mutation of the RVD sequence to RGD. Studies utilizing RGD-containing peptides and well-characterized antibodies to integrins indicated that cell attachment to the third FN type III repeat was mediated by at least two different integrin receptors of the av subtype. Additional cellular receptors may also be involved in cell attachment to CT. For example, an antibody to the beta1 subfamily of integrins partially inhibited binding of cells to intact CT but did not inhibit cell binding to the third FN type III repeat. These findings suggest that the RGD site in CT is able to mediate cell attachment to integrins and thus is not a cryptic adhesion site. They also open the possibility that the functions of CT in processes such as counteradhesion, cell migration, cell proliferation, and cell differentiation may be mediated in part by interaction with multiple integrins.