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

Abstract

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.