Nobile V, Vallee B L, Shapiro R
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4331-5. doi: 10.1073/pnas.93.9.4331.
Angiogenin-related protein (Angrp), the putative product of a recently discovered mouse gene, shares 78% sequence identity with mouse angiogenin (Ang). In the present study, the relationship of Angrp to Ang has been investigated by producing both proteins in bacteria and comparing their functional properties. We find that mouse Ang is potently angiogenic, but Angrp is not, even when assayed at relatively high doses. A deficiency in catalytic capacity, which is essential for the biological activity of Ang, does not appear to underlie Angrp's lack of angiogenicity. In fact, Angrp has somewhat greater ribonucleolytic activity toward tRNA and dinucleotide substrates than does Ang. Instead, an inability to bind cellular receptors is implicated since Angrp does not inhibit Ang-induced angiogenesis. Poor conservation of the Ang receptor recognition sequence 58-69 in Angrp most likely contributes to this defect. However, other substitutions must also influence receptor binding since an Angrp quadruple mutant that is identical to Ang in this segment still lacks both angiogenic activity and the capacity to inhibit Ang. The functional differences between Ang and Angrp, together with evidence presented herein that Angrp is regulated differently than Ang, suggest that the roles of the two proteins in vivo may be quite distinct.
血管生成素相关蛋白（Angrp）是最近发现的一个小鼠基因的推测产物，与小鼠血管生成素（Ang）具有78%的序列同一性。在本研究中，通过在细菌中表达这两种蛋白并比较它们的功能特性，研究了Angrp与Ang之间的关系。我们发现，小鼠Ang具有很强的血管生成活性，但Angrp即使在相对高剂量下检测也没有血管生成活性。对Ang的生物学活性至关重要的催化能力缺陷似乎并不是Angrp缺乏血管生成活性的原因。事实上，Angrp对tRNA和二核苷酸底物的核糖核酸酶活性比Ang略高。相反，由于Angrp不能抑制Ang诱导的血管生成，提示其无法结合细胞受体。Angrp中Ang受体识别序列58 - 69的保守性较差很可能导致了这一缺陷。然而，其他取代也必定影响受体结合，因为在该片段与Ang相同的Angrp四重突变体仍然既缺乏血管生成活性，也缺乏抑制Ang的能力。Ang和Angrp之间的功能差异，以及本文提供的证据表明Angrp与Ang的调节方式不同，提示这两种蛋白在体内的作用可能截然不同。
