The study investigates the effects of ligating the fibronectin receptor (FnR) on gene expression in rabbit synovial fibroblasts. Monoclonal antibodies to the FnR, which block initial adhesion of fibroblasts to fibronectin, induce the expression of genes encoding the secreted extracellular matrix-degrading metalloproteinases, collagenase and stromelysin. This induction is a direct consequence of interaction with the FnR, as shown by the accumulation of mRNA for these genes. Monoclonal antibodies to other membrane glycoprotein receptors do not affect metalloproteinase gene expression. Treatment of fibroblasts with anti-FnR in solution for less than 2 hours triggers gene expression, and this induction is blocked by dexamethasone. Unlike other inducers of metalloproteinase expression, such as phorbol diesters and growth factors, the addition of anti-FnR in solution to cells adherent to serum-derived adhesion proteins or collagen does not cause detectable changes in cell shape or actin microfilament organization. The inductive effects are potentiated by cross-linking of the ligand. Fab fragments of anti-FnR are ineffective unless cross-linked or immobilized on the substrate. Adhesion of fibroblasts to native fibronectin does not induce metalloproteinases, but adhesion to covalently immobilized peptides containing the arg-gly-aspartic acid sequence derived from fibronectin, ranging in size from hexapeptides to 120 kD, induces collagenase and stromelysin gene expression. This suggests that degradation products of fibronectin are the natural inductive ligands for the FnR. These findings demonstrate that signals leading to changes in gene expression are transduced by the FnR, a member of the integrin family of extracellular matrix receptors. The signaling of changes in gene expression by the FnR is distinct from signaling involving cell shape and actin cytoarchitecture. At least two distinct signals are generated: the binding of fibronectin-derived fragments and adhesion-blocking antibodies to the FnR triggers events different from those triggered by binding of the native fibronectin ligand. Because the genes regulated by this integrin are for enzymes that degrade the extracellular matrix, these results suggest that information transduced by the binding of various ligands to integrins may orchestrate the expression of genes regulating cell behavior in the extracellular environment.The study investigates the effects of ligating the fibronectin receptor (FnR) on gene expression in rabbit synovial fibroblasts. Monoclonal antibodies to the FnR, which block initial adhesion of fibroblasts to fibronectin, induce the expression of genes encoding the secreted extracellular matrix-degrading metalloproteinases, collagenase and stromelysin. This induction is a direct consequence of interaction with the FnR, as shown by the accumulation of mRNA for these genes. Monoclonal antibodies to other membrane glycoprotein receptors do not affect metalloproteinase gene expression. Treatment of fibroblasts with anti-FnR in solution for less than 2 hours triggers gene expression, and this induction is blocked by dexamethasone. Unlike other inducers of metalloproteinase expression, such as phorbol diesters and growth factors, the addition of anti-FnR in solution to cells adherent to serum-derived adhesion proteins or collagen does not cause detectable changes in cell shape or actin microfilament organization. The inductive effects are potentiated by cross-linking of the ligand. Fab fragments of anti-FnR are ineffective unless cross-linked or immobilized on the substrate. Adhesion of fibroblasts to native fibronectin does not induce metalloproteinases, but adhesion to covalently immobilized peptides containing the arg-gly-aspartic acid sequence derived from fibronectin, ranging in size from hexapeptides to 120 kD, induces collagenase and stromelysin gene expression. This suggests that degradation products of fibronectin are the natural inductive ligands for the FnR. These findings demonstrate that signals leading to changes in gene expression are transduced by the FnR, a member of the integrin family of extracellular matrix receptors. The signaling of changes in gene expression by the FnR is distinct from signaling involving cell shape and actin cytoarchitecture. At least two distinct signals are generated: the binding of fibronectin-derived fragments and adhesion-blocking antibodies to the FnR triggers events different from those triggered by binding of the native fibronectin ligand. Because the genes regulated by this integrin are for enzymes that degrade the extracellular matrix, these results suggest that information transduced by the binding of various ligands to integrins may orchestrate the expression of genes regulating cell behavior in the extracellular environment.