Isolation of Fibronectin Receptors

Abstract

Fibronectin is an adhesive glycoprotein involved in a variety of cellular functions, including adhesion of cells to extracellular matrices, embryonic cell migration and differentiation, wound healing, and hemostasis (Yamada and Olden, 1978; Hynes, 1985; Ruoslahti and Pierschbacher, 1987; Mosher, 1988). As might be expected for a protein with such varied functions, fibronectin can interact with more than one cell surface receptor. These fibronectin receptors interact with specific peptide recognition sequences in fibronectin, of which there appear to be at least four. Most cell interactions occur with the central fibronectin cell-adhesive domain containing the sequence Gly-Arg-Gly-Asp-Ser (GRGDS) combined with a second crucial site of ≤37 amino acids (Ruoslahti and Pierschbacher, 1987; Obara et al., 1988; Yamada, 1988). The central 3 amino acids of the GRGDS sequence appear to be the most important in this pentapeptide, and receptors that bind to this adhesive recognition sequence are termed RGD receptors. In animal studies, synthetic peptides containing such sequences can block the function of RGD receptors crucial for embryonic cell migration, platelet adhesion and aggregation, and experimental metastasis (reviewed in Yamada, 1988). The RGD sequence appears to require a second, synergistic site for effective interactions with nucleated mammalian cells and to bind the presently best-characterized fibronectin receptor termed α₅β₁ or VLA-5 (Obara et al., 1988,1989).