THE MOUSE VLA-2 HOMOLOG SUPPORTS COLLAGEN AND LAMININ ADHESION BUT NOT VIRUS BINDING

Human VLA-2 (alpha(2) beta(1)) mediates cellular adhesion to collagen and laminin and cell attachment by the human pathogen echovirus 1. We report here the cloning, sequencing and functional expression of the m ouse VLA-2 alpha subunit homologue. This integrin subunit is closely r elated to its human counterpart, with 84% amino acid identity between the human and murine proteins. Conserved structural features include a n identical number of amino acids, the presence of an I domain, and id entity in the number and position of N-linked glycosylation sites and putative divalent cation binding regions. Murine and human alpha(2) sh ow 30% amino acid divergence within the cytoplasmic tail, a difference that can be detected with antisera directed against the C-terminal pe ptides. Functionally, mouse alpha(2) was capable of mediating cell att achment to collagen and laminin, and responded to both intra- and extr acellular signals with changes in its ligand affinity. In contrast, un like its human homologue, mouse alpha(2) did not promote binding of ec hovirus I. Comparison of the primary structure of the homologues leads us to predict that echovirus 1 may bind in the region of the first tw o thirds of the human alpha(2) 1 domain, where the sequences are most divergent, whereas more conserved flanking regions, and the conserved terminal one third of the I domain, may be involved in adhesion to col lagen and laminin.