Kringle 5 causes cell cycle arrest and apoptosis of endothelial cells

Angiostatin which contains the first four kringle domains of plasminogen ha s been documented to be a patent inhibitor of angiogenesis. More recently, another kringle structure within plasminogen but outside angiostatin, known as kringle 5 (K5), was found to inhibit endothelial cell proliferation and migration. Here, we report the cloning and expression of mouse kringle 5 ( rK5) in a bacterial expression system. The protein was purified to homogene ity using a Ni-NTA column, rK5 inhibited both proliferation and migration o f endothelial cells with ED50's of 10 nM and < 500 nn;I, respectively. In a ddition, we show for the first time that rK5 causes cell cycle arrest and a poptosis, shedding further insight into rK5's mechanism of action. Finally, we show that these actions are endothelial cell specific. (C) 1999 Academi c Press.