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.
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.
Hemler
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ME
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Crouse
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C
Sonnenberg
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D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D004848:Epithelium / Q000502:physiology; D006801:Humans; D016023:Integrins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism; D010449:Peptide Mapping; D011233:Precipitin Tests; D016029:Receptors, Very Late Antigen; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D016023:Integrins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D016029:Receptors, Very Late Antigen; D010447:Peptide Hydrolases