Following angiogenin during angiogenesis: A journey from the cell surface to the nucleolus

Angiogenin is a potent inducer of new blood vessel formation. It binds to high-affinity endot helial c ell-surface receptors and, with lower affinity, to extracellular matrix. Angiogenin is the only angiogenic factor k nown to exhibit ribonucleolytic activity. It belongs to the pancreatic RNase superfamily of proteins. Angiogenin is the only member of the superfamily able to stimulate angiogenesis. Although the catalytic activity of the protein i s rather weak, it is critical for its angiogenic properties. Angiogenin is specifically endo cytosed by endothelial c ells and transported to the nucleus, where it accumulates in the nucleolus. Also, the nucle ar location of the a ngiogenic factor appears to be necessary for its angiogenic activity. The mechanism of action of the protein seems to be unusual, since it does not fit into the current paradigm of how exogenous regulatory polypeptides, i ncluding other angiogenic factors, work. Here, the role of transport of angiogenin from the ce ll-surface into the nucleolus and of its intracellular/nuclear mode of action in stimulation of angiogenesis is discussed.