mAngiogenin-3, a target gene of oncoprotein E2a-Pbx1, encodes a new angiogenic member of the angiogenin family.
Angiogenins are proteins in the pancreatic ribonuclease superfamily that utilize their ribonuclease activity to induce formation of new blood vessels. Recently we identified a new member of the angiogenin gene family, mouse angiogenin-3, by virtue of its transcriptional activation in NIH3T3 fibroblasts coincident with transformation by the chimeric leukemia oncogene, E2a-Pbx1. Here we have isolated the cDNA encoding mouse angiogenin-3 and used it to produce the protein in E. coli. We demonstrate that mouse angiogenin-3 is a ribonuclease whose activity and specificity towards tRNA and dinucleotide substrates differ from those of mouse angiogenin or of mouse angiogenin-related protein, a non-angiogenic factor. Mouse angiogenin-3 induced angiogenesis in both the chicken embryo chorioallantoic membrane assay and the rat cremaster muscle. Electron microscopy revealed that endothelial cells within vessels induced by both mouse angiogenin-3 and mouse angiogenin contain fenestrations similar to those observed in endothelial cells from neovasculature induced by vascular endothelial growth factor and basic fibroblast growth factor. Mouse angiogenin-3 also induced other molecular events typical of rapidly proliferating endothelial cells, such as increases in rough endoplasmic reticulum, polysomes, and mitochondria.
Fu
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Department of Pathology, University of California, San Diego, La Jolla 92093-0612, USA.
Roberts
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Nobile
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Shapiro
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Kamps
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D018398:Homeodomain Proteins; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000098:blood supply / Q000196:embryology; D018919:Neovascularization, Physiologic; D015514:Oncogene Proteins, Fusion; D051381:Rats; D012260:Ribonucleases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
C403682:Ang3 protein, mouse; D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion; C089847:E2A-Pbx1 fusion protein; D012260:Ribonucleases