ADDITIONAL RECOGNITION SITES IN THE C-TERMINAL HEPARIN-BINDING DOMAINOF FIBRONECTIN PROMOTE ADHESION OF PMA-TREATED U937 CELLS

Recently we have shown an evidence that a peptide, corresponding to re sidues Gln(1892) to Gly(1910), from the C-terminal heparin-binding dom ain of fibronectin promotes adhesion of phorbol-12-myristate 13-acetat e (PMA)-treated U937 cells and binds to both integrin alpha(4) beta(1) and glycosaminoglycans on U937 cells surface. We present additional a dhesion-promoting sites to PMA-treated U937 cells present in the C-ter minal heparin-binding domain of fibronectin. Three synthetic peptides (residues Ala(1819) to Lys(1830), designated E5; Thr(1828) to Gly(1940 ), E4; and Lys(1946) to Leu(1963), D1) were active to inhibit adhesion of PMA-treated U937 cells to the 29-kDa fragment comprising the C-ter minal heparin-binding domain of fibronectin. Scrambled versions of the se peptides had no inhibitory activity on this adhesion. The IgG-conju gated peptides (IgG-ES, IgG-E4, and IgG-D1) were also active and suppo rted adhesion to an extent comparable to that of the 29-kDa fragment. The adhesion of PMA-treated U937 cells on these three IgG-conjugated p eptides was only inhibited by glycosaminoglycans and not by integrin a lpha(4) beta(1). These results indicate that additional adhesion-promo ting sequences are present in the C-terminal heparin-binding domain of fibronectin and that the activity of these peptides depends on peptid e sequence, mainly the result of net charges or net hydropathy indices . (C) 1998 Elsevier Science Inc.