A synthetic peptide, FN-C/H-V, from the C-terminal heparin-binding domain of fibronectin promotes adhesion of PMA stimulated U937 cells.
Hematopoietic cells differentially bind to the C-terminal heparin-binding domain of fibronectin depending on the activation state of integrin alpha 4 beta 1. In this study, we have identified a synthetic peptide derived from the C-terminal heparin-binding domain of fibronectin that promotes adhesion of PMA-treated U937 cells (a monocytic cell line) in a dose-dependent manner. A peptide (FN-C/H-V; residues Gln1892 to Gly1910) was active to inhibit adhesion of PMA-treated U937 cells to the 29-kDa fragment comprising the C-terminal heparin-binding domain of fibronectin. A peptide with scrambled version of FN-C/H-V lost the inhibitory activity on the adhesion. Furthermore, the IgG-conjugated FN-C/H-V promoted the adhesion of PMA-treated U937 cells to an extent comparable to that of the 29-kDa fragment. The adhesion of PMA-treated U937 cells on IgG-conjugated FN-C/H-V was inhibited both by anti-alpha 4 beta 1 antibody and by glycosaminoglycans including chondroitin sulfate and heparan sulfate. The other peptide, FN-C/H-II, was also a weak adhesion-promoting domain. These results suggest that the amino acid sequence defined by peptide FN-C/H-V contributes to the main adhesion-promoting activity of the 29-kDa fragment of fibronectin to stimulated U937 cells. The regulation of interactions of alpha 4 beta 1 integrin and glycosaminoglycans with ligands in fibronectin may have important implications for the migration and function of U937 cells.
Kato
K
K
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Mohri
H
H
Tamura
T
T
Okubo
T
T
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000276:immunology; D016023:Integrins / Q000276:immunology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; C082338:FN-C-H II peptide; D005353:Fibronectins; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D010446:Peptide Fragments; D016201:Receptors, Lymphocyte Homing; D006493:Heparin; D013755:Tetradecanoylphorbol Acetate