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

J Biol Chem. 2000 Oct 6;275(40):30907-15. doi: 10.1074/jbc.M002752200.


betaig-h3 is a transforming growth factor-beta-inducible cell adhesion molecule that has four characteristic homologous repeated domains. We made recombinant betaig-h3 proteins, which were highly active in mediating human corneal epithelial (HCE) cell adhesion and spreading. The 2nd and the 4th repeated domains were sufficient to mediate HCE cell adhesion. A sequence analysis showed that aspartic acid (Asp) and isoleucine (Ile) of the 2nd and the 4th domains are highly conserved in many fasciclin 1 homologous (fas-1) domains. Substitution mutational study identified these two amino acids are essential for cell adhesion. Synthetic peptides containing Asp and Ile, NKDIL and EPDIM derived from the 2nd and the 4th domains, respectively, almost completely blocked cell adhesion mediated by not only wild type betaig-h3 but also each of the 2nd and the 4th domains. These peptides alone were fully active in mediating cell adhesion. In addition, we demonstrated the functional receptor for betaig-h3 is alpha(3)beta(1) integrin. These results, therefore, establish the essential motifs within the 2nd and the 4th domains of betaig-h3, which interact with alpha(3)beta(1) integrin to mediate HCE cell adhesion to betaig-h3 and suggest that other proteins containing Asp-Ile in their fas-1 domains could possibly function as cell adhesion molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aspartic Acid / chemistry
  • Cell Adhesion
  • Cell Separation
  • Conserved Sequence
  • Cornea / cytology
  • Cornea / metabolism
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Epithelial Cells / cytology
  • Extracellular Matrix Proteins*
  • Fibronectins / pharmacology
  • Flow Cytometry
  • Humans
  • Integrins / chemistry
  • Integrins / metabolism
  • Isoleucine / chemistry
  • K562 Cells
  • Models, Genetic
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / genetics*
  • Peptides / metabolism
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Serum Albumin, Bovine / pharmacology
  • Transfection
  • Transforming Growth Factor beta / metabolism*


  • DNA, Complementary
  • Extracellular Matrix Proteins
  • Fibronectins
  • Integrins
  • Neoplasm Proteins
  • Peptides
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Isoleucine
  • betaIG-H3 protein
  • Serum Albumin, Bovine
  • Aspartic Acid