Identification of motifs for cell adhesion within the repeated domains of transforming growth factor-beta-induced gene, beta ig-h3

beta ig-h3 is a transforming growth factor-beta-inducible cell adhesion mol ecule that has four characteristic homologous repeated domains. We made rec ombinant beta ig-h3 proteins, which were highly active in mediating human c orneal epithelial (HCE) cell adhesion and spreading. The 2nd and the 4th re peated domains were sufficient to mediate HCE cell adhesion, A sequence ana lysis showed that aspartic acid (Asp) and isoleucine (Ile) of the 2nd and t he 4th domains are highly conserved in many fasciclin 1 homologous (fas-l) domains, Substitution mutational study identified these two amino acids are essential for cell adhesion. Synthetic peptides containing Asp and Re, NKD IL and EPDIM derived from the 2nd and the 4th domains, respectively, almost completely blocked cell adhesion mediated by not only wild type beta ig-h3 but also each of the 2nd and the 4th domains. These peptides alone were fu lly active in mediating cell adhesion. In addition, we demonstrated the fun ctional receptor for beta ig-h3 is alpha(3)beta(1) integrin. These results, therefore, establish the essential motifs within the 2nd and the 4th domai ns of beta ig-h3, which interact with alpha(3)beta(1) integrin to mediate H CE cell adhesion to beta ig-h3 and suggest that other proteins containing A sp-ne in their fas-l domains could possibly function as cell adhesion molec ules.