CHARACTERIZATION OF MOUSE ANGIOGENIN-RELATED PROTEIN - IMPLICATIONS FOR FUNCTIONAL-STUDIES ON ANGIOGENIN

Angiogenin-related protein (Angrp); the putative product of a recently discovered mouse gene, shares 78% sequence identity with mouse angiog enin (Ang). In the present study, the relationship of Angrp to Ang has been investigated by producing both proteins in bacteria and comparin g their functional properties. We find that mouse Ang is potently angi ogenic, but Angrp is not, even when assayed at relatively high doses. A deficiency in catalytic capacity, which is essential for the biologi cal activity of Ang, does not appear to underlie Angrp's lack of angio genicity. In fact, Angrp has somewhat greater ribonucleolytic activity toward tRNA and dinucleotide substrates than does Ang. Instead, an in ability to bind cellular receptors is implicated since Angrp does not inhibit Ang-induced angiogenesis. Poor conservation of the Ang recepto r recognition sequence 58-69 in Angrp most likely contributes to this defect. However, other substitutions must also influence receptor bind ing since an Angrp quadruple mutant that is identical to Ang in this s egment still Lacks both angiogenic activity and the capacity to inhibi t Ang. The functional differences between Ang and Angrp, together with evidence presented herein that Angrp is regulated differently than An g, suggest that the roles of the two proteins in vivo may be quite dis tinct.