The alpha 6 beta 1 (VLA-6) and alpha 6 beta 4 protein complexes: tissue distribution and biochemical properties

Abstract

A member of the integrin family, the alpha 6 beta 4 complex was previously identified on human and mouse carcinoma cell lines by using a rat monoclonal antibody to alpha 6. Here we describe two monoclonal antibodies that recognize epitopes on the beta 4 subunit of the human and mouse alpha 6 beta 4 complexes. The monoclonal antibodies against beta 4 were able to preclear alpha 6 beta 4, but not alpha 6 beta 1 from cell line extracts. A substantial fraction of the total beta 4 subunits present on the cell surface was not associated with alpha 6, as it could not be removed by anti-alpha 6 antibodies, but remained precipitable with anti-beta 4 antibodies. There was no evidence for novel alpha subunits associated with beta 4. The alpha 6 subunit consists of disulfide-linked heavy and light chains. The variability in size of these two chains from different cell types is largely due to differences in modifications of N-linked glycans. Additional heterogeneity may be caused by differential proteolytic cleavage of the alpha 6 precursor. Immunoperoxidase staining of tissue sections of neonatal and adult mice revealed that beta 4 expression is limited to epithelial tissues and peripheral nerves. The alpha 6 subunit has a wider distribution that includes all tissues and cells stained by antibodies against beta 4. Cells and tissue that are positive for alpha 6, but negative for beta 4, may express the alpha 6 beta 1 complex.