Characterization of the integrin alpha v beta 6 as a fibronectin-binding protein.
Characterization of the integrin alpha v beta 6 as a fibronectin-binding protein.
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DOI：
10.1016/s0021-9258(18)42622-1
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发表时间：
1992-03
期刊：
影响因子：
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通讯作者：
M. Busk;R. Pytela;D. Sheppard
中科院分区：
文献类型：
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作者：
M. Busk;R. Pytela;D. Sheppard
整合素是由一个α亚基和一个β亚基彼此非共价结合组成的二价阳离子依赖性细胞粘附受体的复杂家族。整联蛋白的一个亚组含有与几个β亚基（例如β 3、β 5、β 1）之一相关的α v亚基。我们最近发现了一种新的整合素β亚基，β 6，这是目前在一些上皮细胞系。使用针对β 6羧基末端肽的多克隆抗体，我们现在已经确定了整合素异源二聚体，α v β 6，在两个人癌细胞系的表面上。使用胰腺癌细胞系FG-2的裂解物的亲和层析，我们证明α v β 6与纤连蛋白结合，但不与玻连蛋白或胶原I结合。相比之下，α v β 5整联蛋白（也在FG-2细胞上表达）仅与玻连蛋白结合。固定化胶原I不与α v整联蛋白相互作用，但结合含β 1的整联蛋白。α v β 6和α v β 5通过含有序列Arg-Gly-Asp（RGD）的六肽从其各自的固定化配体洗脱。RGD在Ca 2+存在下非常有效，在Mg 2+中稍微不那么有效，并且在Mn 2+中几乎无活性。这些结果表明，在FG-2癌细胞中，α v β 6作为RGD依赖性纤连蛋白受体起作用。与此观点一致，细胞粘附试验表明，FG-2细胞附着到纤连蛋白仅部分抑制抗β 1整联蛋白抗体，这意味着其他纤连蛋白受体可能参与。结合最近关于α v β 5的玻连蛋白受体功能的报道，我们的结果表明先前描述的癌细胞整联蛋白α v β x（Cheresh，D. A.、史密斯，J.W.，库珀，H。M.，和Quaranta，V.（1989）Cell 57，59-69）是至少两种不同受体的混合物：α v β 5，介导与玻连蛋白的粘附，和α v β 6，介导与纤连蛋白的粘附。
Integrins are a complex family of divalent cation-dependent cell adhesion receptors composed of one alpha and one beta subunit noncovalently bound to one another. A subset of integrins contains the alpha v subunit in association with one of several beta subunits (e.g. beta 3, beta 5, beta 1). We have recently identified a novel integrin beta subunit, beta 6, that is present in a number of epithelial cell lines. Using a polyclonal antibody raised against the carboxyl-terminal peptide of beta 6, we have now identified the integrin heterodimer, alpha v beta 6, on the surface of two human carcinoma cell lines. Using affinity chromatography of lysates from the pancreatic carcinoma cell line, FG-2, we demonstrate that alpha v beta 6 binds to fibronectin, but not to vitronectin or collagen I. In contrast, the alpha v beta 5 integrin, which is also expressed on FG-2 cells, binds exclusively to vitronectin. Immobilized collagen I does not interact with alpha v integrins, but binds beta 1-containing integrins. Both alpha v beta 6 and alpha v beta 5 are eluted from their respective immobilized ligands by a hexa-peptide containing the sequence Arg-Gly-Asp (RGD). RGD is highly effective in the presence of Ca2+, somewhat less effective in Mg2+, and virtually inactive in Mn2+. These results suggest that alpha v beta 6 functions as an RGD-dependent fibronectin receptor in FG-2 carcinoma cells. In agreement with this notion, cell adhesion assays show that FG-2 cell attachment to fibronectin is only partially inhibited by anti-beta 1 integrin antibodies, implying that other fibronectin receptors may be involved. Taken together with recent reports on the vitronectin receptor function of alpha v beta 5, our results suggest that the previously described carcinoma cell integrin, alpha v beta x (Cheresh, D. A., Smith, J. W., Cooper, H. M., and Quaranta, V. (1989) Cell 57, 59-69), is a mixture of at least two different receptors: alpha v beta 5, mediating adhesion to vitronectin, and alpha v beta 6, mediating adhesion to fibronectin.