text: Angiogenin is a key protein implicated in angiogenesis in normal and tumor growth. Angiogenin interacts with endothelial and smooth muscle cells resulting in cell migration, invasion, proliferation and formation of tubular structures. Ang binds to actin of both smooth muscle and endothelial cells to form complexes that activate proteolytic cascades which upregulate the production of proteases and plasmin that degrade the laminin and fibronectin layers of the basement membrane. Degradation of the basement membrane and extracellular matrix allows the endothelial cells to penetrate and migrate into the perivascular tissue. Signal transduction pathways activated by Ang interactions at the cellular membrane of endothelial cells produce extracellular signal-related kinase1/2 (ERK1/2) and protein kinase B/Akt. Activation of these proteins leads to invasion of the basement membrane and cell proliferation associated with further angiogenesis. The most important step in the angiogenesis process is the translocation of Ang to the cell nucleus. Once Ang has been translocated to the nucleus, it enhances rRNA transcription by binding to the CT-rich (CTCTCTCTCTCTCTCTCCCTC) angiogenin binding element (ABE) within the upstream intergenic region of rDNA, which subsequently activates other angiogenic factors that induce angiogenesis.
  However, angiogenin is unique among the many proteins that are involved in angiogenesis in that it is also an enzyme with an amino acid sequence 33% identical to that of bovine pancreatic ribonuclease (RNase A). Ang has the same general catalytic properties as RNase A, it cleaves preferentially on the 3' side of pyrimidines and follows a transphosphorylation/hydrolysis mechanism. Although angiogenin contains many of the same catalytic residues as RNase A, it cleaves standard RNA substrates 10–10 times less efficiently than RNase A. The reason for this inefficiency is due to the 117 residue consisting of a glutamine, which blocks the catalytic site. Removal of this residue through mutation increases the ribonuclease activity between 11 and 30 fold. Despite this apparent weakness, the enzymatic activity of Ang appears to be essential for biological activity: replacements of important catalytic site residues (histidine-13 and histidine-114) invariably diminish both the ribonuclease activity toward tRNA by 10,000 fold and almost abolishes angiogenesis activities completely.