CYR61, A PRODUCT OF A GROWTH FACTOR-INDUCIBLE IMMEDIATE-EARLY GENE, PROMOTES CELL-PROLIFERATION, MIGRATION, AND ADHESION

cyr61 was first identified as a growth factor-inducible immediate-earl y gene in mouse fibroblasts. The encoded Cyr61 protein is a secreted, cysteine-rich heparin-binding protein that associates with the cell su rface and the extracellular matrix, and in these aspects it resembles the Wnt-1 protein and a number of known growth factors, During embryog enesis, cyr61 is expressed most notably in mesenchymal cells that are differentiating into chondrocytes and in the vessel walls of the devel oping circulatory system, cyr61 is a member of an emerging gene family that encodes growth regulators, including the connective tissue growt h factor and an avian proto-oncoprotein, Nov, cyr61 also shares sequen ce similarities with two Drosophila genes, twisted gastrulation and sh ort gastrulation, which interact with decapentaplegic to regulate dors al-ventral patterning. In this report we describe the purification of the Cyr61 protein in a biologically active form, and we show that puri fied Cyr61 has the following activities: (i) it promotes the attachmen t and spreading of endothelial cells in a manner similar to that of fi bronectin; (ii) it enhances the effects of basic fibroblast growth fac tor and platelet derived growth factor on the rate of DNA synthesis of fibroblasts and vascular endothelial cells, although it has no detect able mitogenic activity by itself; and (iii) it acts as a chemotactic factor for fibroblasts. Taken together, these activities indicate that Cyr61 is likely to function as an extracellular matrix signaling mole cule rather than as a classical growth factor and may regulate process es of cell proliferation, migration, adhesion, and differentiation dur ing development.