Abstract

Connective tissue growth factor (CTGF) is a 349-residue mosaic protein that contains four structural modules implicated in protein-protein interactions. To address the functionality of residues 247-349 (containing module 4 alone), this region of CTGF was produced as a maltose binding protein (MBP) fusion protein in E. coli. After removal of MBP, recombinant CTGF commenced at Glu(247), was of M(r) 10 000, was immunoreactive with anti-CTGF[247-260], bound strongly to heparin, and promoted dose-dependent adhesion of fibroblasts, myofibroblasts, endothelial cells, and epithelial cells. An 8 kDa presumptive C-terminally truncated form of CTGF commencing at Glu(247) also promoted cell adhesion. CTGF-mediated cell adhesion was abolished by heparin or EDTA. These data demonstrate the presence of heparin-binding and cell-adhesion motifs within the C-terminal 103 residues of CTGF and show that CTGF-mediated cell adhesion is heparin-and divalent cation-dependent. Thus, CTGF isoforms comprising essentially module 4 are intrinsically functional in the absence of the other constituent modules of CTGF.