The angiogenins

Abstract

The angiogenic and other biological functions of the angiogenins, members of the pancreatic RNase superfamily of proteins, are reviewed in the context of their primary and tertiary structures. The ribonucleolytic activity and interactions with the placental ribonuclease inhibitor have seen much study in the last few years. The mechanism of the angiogenic activity of angiogenin has recently been postulated as involving multiple interactions with other proteins through specific regions on the molecular surface of angiogenin. These molecular partners include heparin, plasminogen, elastase, angiostatin, actin and most importantly a 170-kilodalton receptor on subconfluent endothelial cells. The existence of the latter receptor was established in conjunction with a mitogenic activity of angiogenin on subconfluent cells. The levels of angiogenin in various physiological and disease states are summarized, including various studies on pregnancy and angiogenin. Correlations are seen between states of enhanced angiogenesis and angiogenin levels. An overview of the relationship of angiogenin and the other RNases of the superfamily showed that their genes all are in relative close proximity on human chromosome 14. Examination of the many expressed sequence tags published in the public databanks, for angiogenin and the other RNases, revealed that angiogenin and RNase-4 (the most evolutionarily conserved RNase), share various identical 5'-untranslated regions on their sets of messenger RNAs, suggesting that their genes are in very close proximity on chromosome 14 and that they are products of differential splicing. This in turn suggests that, in both humans and mice, expression of these two proteins is under identical control, with obvious implications for their biological activities. The evolutionary history of the angiogenins is examined briefly on the basis of the protein sequences of the human, rabbit, pig, two bovine and four mouse angiogenins, and two mouse angiogenin pseudogene sequences. The discrepancy between the conventional requirement for conservatism in structure to allow multimolecule interactions, and the actual fast-changing sequence of the angiogenins, in concert with the wide-ranging activity even in birds, of human angiogenin, is discussed.

Isolation, Characterization, and Evolutionary Divergence of Mouse RNase 6: Evidence for Unusual Evolution in Rodents

“…Angiogenin (RNase 5) is structurally distinct in that it has only six of the canonical eight cysteines. It was originally identified as a factor stimulating blood vessel growth (Strydom 1998). Most recently, mouse and human angiogenins have been identified as microbicidal agents against both bacteria and fungi, suggesting that angiogenins con-tribute to innate host defenses (Hooper et al 2003).…”

Evolution and Function of Leukocyte RNase A Ribonucleases of the Avian Species, Gallus gallus

“…RNase A ribonucleases have been implicated in a wide variety of physiologic functions and have been observed to promote angiogenesis, cellular apoptosis, and anti-tumor and anti-pathogen host defense via a complex array of seemingly unrelated molecular mechanisms (reviewed in Refs. [1][2][3][4][5][6][7][8].…”

A novel way of therapeutic angiogenesis using an adeno-associated virus-mediated angiogenin gene transfer

“…ANG1, however, has not been tested as an angiogenesis therapy (Strydom, 1998;Pavlov and Badet, 2001). Among viral gene delivery systems, such as retrovirus, adenovirus, AAV, and lentivirus, AAV is regarded as one of the best if the size of the therapeutic gene is small enough for rAAV to be packaged efficiently (Lundstrom, 2003).…”