Human CYR61-mediated enhancement of bFGF-induced DNA synthesis in human umbilical vein endothelial cells

Abstract

CYR61 is a member of an emerging family of growth regulators that includes the human connective tissue growth factor and the chicken protooncoprotein Nov. Encoded by a growth factor-inducible immediate-early gene, CYR61 is a secreted, cysteine-rich heparin-binding protein that associates with the extracellular matrix and cell surface. In this report, we describe the cloning of the human hCYR61 cDNA and expression and purification of the hCYR61 protein. The hCYR61 mRNA is abundant in the heart, lung, pancreas and placenta, is present at a low level in skeletal muscle and brain and is not detectable in liver and kidney. Purified recombinant hCYR61 protein does not induce thymidine incorporation in human umbilical vein endothelial cells by itself, but enhances bFGF-induced DNA synthesis. We show that hCYR61 acts in this cell system in part by displacement of bFGF bound to the extracellular matrix, thus increasing the effective concentration of bFGF. Possible biological implications of these observations are discussed.