Association of the VLA alpha 6 subunit with a novel protein. A possible alternative to the common VLA beta 1 subunit on certain cell lines.
Association of the VLA alpha 6 subunit with a novel protein. A possible alternative to the common VLA beta 1 subunit on certain cell lines.
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发表时间：
1989-04
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通讯作者：
M. Hemler;C. Crouse;Arnoud Sonnenberg
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作者：
M. Hemler;C. Crouse;Arnoud Sonnenberg
在血小板和其他细胞类型上，VLA-6是典型的整合素异源二聚体，具有α 6- β 1亚基关联。然而，在结肠癌细胞系和其他上皮细胞上，α 6亚基与一种新的蛋白（称为β 4）而不是与VLA β 1亚基结合。β 4蛋白与β 1蛋白不同，因为(i)它不被抗β 1抗体识别，（ii）它产生不同的V8蛋白酶裂解产物，（iii）它具有更有限的细胞分布，（iv）它有多种形式，每种形式都比β 1大，(v)它容易被蛋白酶消化，而对β 1没有影响。尽管在许多方面有所不同，但β 4亚基确实与已经定义的整合素β 1、β 2和β 3亚基具有部分n端序列相似性。通过β 4与抗α 6抗体共沉淀和共价交联实验证实了α 6- β 4复合物的存在。虽然α 6- β 4复合物存在于某些细胞上，但这些细胞上的其他VLA α亚基仍然与VLA β 1亚基相关，形成典型的VLA异源二聚体（如VLA-1、VLA-2、VLA-3）。根据n端氨基酸测序、抗体识别、V8肽图和还原/非还原凝胶迁移的标准，与β 4相关的α 6亚基与血小板和其他细胞类型上与VLA β 1亚基相关的α 6相同。β 4亚基可能是重要的，因为(i)它在结肠癌细胞系表面上非常丰富，（ii）相对于其他表面蛋白，它具有高度的免疫原性。
On platelets and other cell types, VLA-6 is a typical integrin heterodimer, with alpha 6-beta 1 subunit association. However, on colon carcinoma cell lines and other epithelial cells the alpha 6 subunit associates with a novel protein (called beta 4) rather than the VLA beta 1 subunit. The beta 4 protein differs from beta 1 because (i) it is not recognized by anti-beta 1 antibodies, (ii) it yields different V8 protease cleavage products, (iii) it has a more limited cell distribution, (iv) it has multiple forms, each larger in size than beta 1, and (v) it is susceptible to protease digestion which does not effect beta 1. Although different in many respects, the beta 4 subunit does have partial N-terminal sequence similarity to the already defined integrin beta 1, beta 2, and beta 3 subunits. The presence of alpha 6-beta 4 complexes was demonstrated by coprecipitation of beta 4 with an anti-alpha 6 antibody and by covalent cross-linking experiments. Although alpha 6-beta 4 complexes were present on certain cells, other VLA alpha subunits on those same cells remained associated with the VLA beta 1 subunit to form typical VLA heterodimers (e.g. VLA-1, VLA-2, VLA-3). By the criteria of N-terminal amino acid sequencing, antibody recognition, V8 peptide maps, and reduced/nonreduced gel migration, the alpha 6 subunit which associates with beta 4 appears identical to the alpha 6 associated with the VLA beta 1 subunit on platelets and other cell types. The beta 4 subunit may be of major importance because (i) it is highly abundant on the surface of colon carcinoma cell lines, and (ii) it is highly immunogenic relative to other surface proteins.