HUMAN CYR61-MEDIATED ENHANCEMENT OF BFGF-INDUCED DNA-SYNTHESIS IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

CYR61 is a member of an emerging family of growth regulators that incl udes the human connective tissue growth factor and the chicken protoon coprotein Nov, Encoded by a growth factor-inducible immediate-early ge ne, CYR61 is a secreted, cysteine-rich heparin-binding protein that as sociates with the extracellular matrix and cell surface. In this repor t, we describe the cloning of the human hCYR61 cDNA and expression and purification of the hCYR61 protein. The hCYR61 mRNA is abundant in th e heart, lung, pancreas and placenta, is present at a low level in ske letal muscle and brain and is not detectable in liver and kidney, Puri fied recombinant hCYR61 protein does not induce thymidine incorporatio n in human umbilical vein endothelial cells by itself, but enhances bF GF-induced DNA synthesis. We show that hCYR61 acts in this cell system in part by displacement of bFGF bound to the extracellular matrix. th us increasing the effective concentration of bFGF, Possible biological implications of these observations are discussed.