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 endothelial cell-surface receptors and, with lower affinity, to extracellular matrix. Angiogenin is the only angiogenic factor known 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 is rather weak, it is critical for its angiogenic properties. Angiogenin is specifically endocytosed by endothelial cells and transported to the nucleus, where it accumulates in the nucleolus. Also, the nuclear location of the angiogenic 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, including other angiogenic factors, work. Here, the role of transport of angiogenin from the cell-surface into the nucleolus and of its intracellular/nuclear mode of action in stimulation of angiogenesis is discussed.